Logo MitImpact
Home Description Output legend Molecular Dynamics How to cite License

8411 (A > C)

General info

Mitimpact ID
MI.1542
Chr
chrM
Start
8411
Ref
A
Alt
C
Gene symbol
MT-ATP8 Extended gene annotation
Gene position
46
Gene start
8366
Gene end
8572
Gene strand
+
Codon substitution
ATA/CTA
AA pos
16
AA ref
M
AA alt
L
Functional effect
missense
OMIM ID
516070
HGVS
NC_012920.1:g.8411A>C
HGNC ID
7415
RC complex
V
Ensembl gene ID
ENSG00000228253
Ensembl protein ID
ENSP00000355265
Ensembl transcript ID
ENST00000361851
Uniprot ID
P03928
Uniprot name
ATP8_HUMAN
Ncbi gene ID
4509
Ncbi protein ID
YP_003024030.1
Powered by NGL Viewer
Powered by MitoWheel

Conservation

PhyloP 100v
0.789 Conservation Score
PhyloP 470way
0.929 Conservation Score
PhastCons 100v
0.002 Conservation Score
PhastCons 470way
0.009 Conservation Score

Pathogenicity predictors

PolyPhen2
Possibly damaging Score and details of the predictor
SIFT
Neutral Score and details of the predictor
SIFT4G
Damaging Score and details of the predictor
VEST
Neutral Score and details of the predictor
MitoClass 1
Damaging Score and details of the predictor
SNPDryad
Neutral Score and details of the predictor
MutationTaster
.
fathmm
.
AlphaMissense
Likely benign Score and details of the predictor
CADD
Deleterious Score and details of the predictor
PROVEAN
Damaging Score and details of the predictor
Mutation Assessor
.
EFIN SP
Neutral Score and details of the predictor
EFIN HD
Neutral Score and details of the predictor
MLC
Neutral Score and details of the predictor
PANTHER
.
PhD-SNP
.

Pathogenicity meta-predictors

APOGEE1
Neutral Score and details of the meta-predictor
APOGEE2
Likely-benign Score and details of the meta-predictor
CAROL
Neutral Score and details of the meta-predictor
Condel
Deleterious Score and details of the meta-predictor
COVEC WMV
.
MtoolBox
Deleterious Score and details of the meta-predictor
DEOGEN2
.
Meta SNP
.

Cancer-specific predictors

PolyPhen2 transf
Low impact Score and details of the cancer-specific predictor
SIFT transf
Medium impact Score and details of the cancer-specific predictor
MutationAssessor transf
Medium impact Score and details of the cancer-specific predictor
CHASM
Neutral Score and details of the cancer-specific predictor

Databases of Frequencies and Phenotypes

Clinvar ID
692847
Clinvar ALLELEID
681383
Clinvar CLNDISDB
Mondo:mondo:0009723, medgen:c0023264, omim:256000, orphanet:506
Clinvar CLNDN
Leigh syndrome
Clinvar CLNSIG
Uncertain significance
MITOMAP Allele
8411A>C
MITOMAP Disease Clinical info
.
MITOMAP Disease Status
.
MITOMAP Disease Hom/Het
./.
MITOMAP General GenBank Freq
0.0016%
MITOMAP General GenBank Seqs
1
MITOMAP General GenBank Curated refs
.
MITOMAP Variant Class
polymorphism
Gnomad AN
56434
Gnomad AC hom
2
Gnomad AF hom
3.54e-05
Gnomad AC het
0
Gnomad AF het
0.0
Gnomad filter
Pass
HelixMTdb AC hom
16
HelixMTdb AF hom
8.16e-05
HelixMTdb AC het
1
HelixMTdb AF het
5.1e-06
HelixMTdb mean ARF
0.82387
HelixMTdb max ARF
0.82387
ToMMo JPN54K AC
.
ToMMo JPN54K AF
.
ToMMo JPN54K AN
.
COSMIC 90
.
dbSNP 156
.

Residue interaction

EVmutation
Site A-B InterP
Site A-B IntraP
ΔΔG intra
ΔΔG intra interface
ΔΔG inter

Compensated Pathogenic Deviations

Frequency
.
AA ref
.
CPD AA alt
.
Aln pos
.
RefSeq protein ID
.
Species name
.
Ncbi taxon ID
.

8411 (A > G)

General info

Mitimpact ID
MI.1540
Chr
chrM
Start
8411
Ref
A
Alt
G
Gene symbol
MT-ATP8 Extended gene annotation
Gene position
46
Gene start
8366
Gene end
8572
Gene strand
+
Codon substitution
ATA/GTA
AA pos
16
AA ref
M
AA alt
V
Functional effect
missense
OMIM ID
516070
HGVS
NC_012920.1:g.8411A>G
HGNC ID
7415
RC complex
V
Ensembl gene ID
ENSG00000228253
Ensembl protein ID
ENSP00000355265
Ensembl transcript ID
ENST00000361851
Uniprot ID
P03928
Uniprot name
ATP8_HUMAN
Ncbi gene ID
4509
Ncbi protein ID
YP_003024030.1
Powered by NGL Viewer
Powered by MitoWheel

Conservation

PhyloP 100v
0.789 Conservation Score
PhyloP 470way
0.929 Conservation Score
PhastCons 100v
0.002 Conservation Score
PhastCons 470way
0.009 Conservation Score

Pathogenicity predictors

PolyPhen2
Possibly damaging Score and details of the predictor
SIFT
Neutral Score and details of the predictor
SIFT4G
Damaging Score and details of the predictor
VEST
Neutral Score and details of the predictor
MitoClass 1
Neutral Score and details of the predictor
SNPDryad
Neutral Score and details of the predictor
MutationTaster
.
fathmm
.
AlphaMissense
Likely benign Score and details of the predictor
CADD
Neutral Score and details of the predictor
PROVEAN
Damaging Score and details of the predictor
Mutation Assessor
Medium Score and details of the predictor
EFIN SP
Neutral Score and details of the predictor
EFIN HD
Neutral Score and details of the predictor
MLC
Neutral Score and details of the predictor
PANTHER
.
PhD-SNP
.

Pathogenicity meta-predictors

APOGEE1
Neutral Score and details of the meta-predictor
APOGEE2
Likely-benign Score and details of the meta-predictor
CAROL
Neutral Score and details of the meta-predictor
Condel
Neutral Score and details of the meta-predictor
COVEC WMV
.
MtoolBox
Deleterious Score and details of the meta-predictor
DEOGEN2
.
Meta SNP
.

Cancer-specific predictors

PolyPhen2 transf
Low impact Score and details of the cancer-specific predictor
SIFT transf
Medium impact Score and details of the cancer-specific predictor
MutationAssessor transf
Medium impact Score and details of the cancer-specific predictor
CHASM
Neutral Score and details of the cancer-specific predictor

Databases of Frequencies and Phenotypes

Clinvar ID
692848
Clinvar ALLELEID
681384
Clinvar CLNDISDB
Mondo:mondo:0009723, medgen:c0023264, omim:256000, orphanet:506
Clinvar CLNDN
Leigh syndrome
Clinvar CLNSIG
Uncertain significance
MITOMAP Allele
8411A>G
MITOMAP Disease Clinical info
Severe mitochondrial disorder
MITOMAP Disease Status
Reported
MITOMAP Disease Hom/Het
+/-
MITOMAP General GenBank Freq
0.0033%
MITOMAP General GenBank Seqs
2
MITOMAP General GenBank Curated refs
20207608
MITOMAP Variant Class
polymorphism;disease
Gnomad AN
56432
Gnomad AC hom
3
Gnomad AF hom
5.31e-05
Gnomad AC het
2
Gnomad AF het
3.54e-05
Gnomad filter
Pass
HelixMTdb AC hom
2
HelixMTdb AF hom
1.02e-05
HelixMTdb AC het
3
HelixMTdb AF het
1.53e-05
HelixMTdb mean ARF
0.52633
HelixMTdb max ARF
0.72034
ToMMo JPN54K AC
3
ToMMo JPN54K AF
5.5e-05
ToMMo JPN54K AN
54302
COSMIC 90
.
dbSNP 156
.

Residue interaction

EVmutation
Site A-B InterP
Site A-B IntraP
ΔΔG intra
ΔΔG intra interface
ΔΔG inter

Compensated Pathogenic Deviations

Frequency
.
AA ref
.
CPD AA alt
.
Aln pos
.
RefSeq protein ID
.
Species name
.
Ncbi taxon ID
.

8411 (A > T)

General info

Mitimpact ID
MI.1541
Chr
chrM
Start
8411
Ref
A
Alt
T
Gene symbol
MT-ATP8 Extended gene annotation
Gene position
46
Gene start
8366
Gene end
8572
Gene strand
+
Codon substitution
ATA/TTA
AA pos
16
AA ref
M
AA alt
L
Functional effect
missense
OMIM ID
516070
HGVS
NC_012920.1:g.8411A>T
HGNC ID
7415
RC complex
V
Ensembl gene ID
ENSG00000228253
Ensembl protein ID
ENSP00000355265
Ensembl transcript ID
ENST00000361851
Uniprot ID
P03928
Uniprot name
ATP8_HUMAN
Ncbi gene ID
4509
Ncbi protein ID
YP_003024030.1
Powered by NGL Viewer
Powered by MitoWheel

Conservation

PhyloP 100v
0.789 Conservation Score
PhyloP 470way
0.929 Conservation Score
PhastCons 100v
0.002 Conservation Score
PhastCons 470way
0.009 Conservation Score

Pathogenicity predictors

PolyPhen2
Possibly damaging Score and details of the predictor
SIFT
Neutral Score and details of the predictor
SIFT4G
Damaging Score and details of the predictor
VEST
Neutral Score and details of the predictor
MitoClass 1
Damaging Score and details of the predictor
SNPDryad
Neutral Score and details of the predictor
MutationTaster
.
fathmm
.
AlphaMissense
Likely benign Score and details of the predictor
CADD
Deleterious Score and details of the predictor
PROVEAN
Damaging Score and details of the predictor
Mutation Assessor
.
EFIN SP
Neutral Score and details of the predictor
EFIN HD
Neutral Score and details of the predictor
MLC
Neutral Score and details of the predictor
PANTHER
.
PhD-SNP
.

Pathogenicity meta-predictors

APOGEE1
Neutral Score and details of the meta-predictor
APOGEE2
Likely-benign Score and details of the meta-predictor
CAROL
Neutral Score and details of the meta-predictor
Condel
Deleterious Score and details of the meta-predictor
COVEC WMV
.
MtoolBox
Deleterious Score and details of the meta-predictor
DEOGEN2
.
Meta SNP
.

Cancer-specific predictors

PolyPhen2 transf
Low impact Score and details of the cancer-specific predictor
SIFT transf
Medium impact Score and details of the cancer-specific predictor
MutationAssessor transf
Medium impact Score and details of the cancer-specific predictor
CHASM
Neutral Score and details of the cancer-specific predictor

Databases of Frequencies and Phenotypes

Clinvar ID
.
Clinvar ALLELEID
.
Clinvar CLNDISDB
.
Clinvar CLNDN
.
Clinvar CLNSIG
.
MITOMAP Allele
8411A>T
MITOMAP Disease Clinical info
.
MITOMAP Disease Status
.
MITOMAP Disease Hom/Het
./.
MITOMAP General GenBank Freq
.
MITOMAP General GenBank Seqs
.
MITOMAP General GenBank Curated refs
.
MITOMAP Variant Class
.
Gnomad AN
0
Gnomad AC hom
0
Gnomad AF hom
0.0
Gnomad AC het
.
Gnomad AF het
.
Gnomad filter
.
HelixMTdb AC hom
0
HelixMTdb AF hom
0.0
HelixMTdb AC het
.
HelixMTdb AF het
0.0
HelixMTdb mean ARF
0.0
HelixMTdb max ARF
.
ToMMo JPN54K AC
.
ToMMo JPN54K AF
.
ToMMo JPN54K AN
.
COSMIC 90
.
dbSNP 156
.

Residue interaction

EVmutation
Site A-B InterP
Site A-B IntraP
ΔΔG intra
ΔΔG intra interface
ΔΔG inter

Compensated Pathogenic Deviations

Frequency
.
AA ref
.
CPD AA alt
.
Aln pos
.
RefSeq protein ID
.
Species name
.
Ncbi taxon ID
.
~ 8411 (A/C) 8411 (A/G) 8411 (A/T)
~ 8411 (ATA/CTA) 8411 (ATA/GTA) 8411 (ATA/TTA)
MitImpact id MI.1542 MI.1540 MI.1541
Chr chrM chrM chrM
Start 8411 8411 8411
Ref A A A
Alt C G T
Gene symbol MT-ATP8 MT-ATP8 MT-ATP8
Extended annotation mitochondrially encoded ATP synthase membrane subunit 8 mitochondrially encoded ATP synthase membrane subunit 8 mitochondrially encoded ATP synthase membrane subunit 8
Gene position 46 46 46
Gene start 8366 8366 8366
Gene end 8572 8572 8572
Gene strand + + +
Codon substitution ATA/CTA ATA/GTA ATA/TTA
AA position 16 16 16
AA ref M M M
AA alt L V L
Functional effect general missense missense missense
Functional effect detailed missense missense missense
OMIM id 516070 516070 516070
HGVS NC_012920.1:g.8411A>C NC_012920.1:g.8411A>G NC_012920.1:g.8411A>T
HGNC id 7415 7415 7415
Respiratory Chain complex V V V
Ensembl gene id ENSG00000228253 ENSG00000228253 ENSG00000228253
Ensembl transcript id ENST00000361851 ENST00000361851 ENST00000361851
Ensembl protein id ENSP00000355265 ENSP00000355265 ENSP00000355265
Uniprot id P03928 P03928 P03928
Uniprot name ATP8_HUMAN ATP8_HUMAN ATP8_HUMAN
Ncbi gene id 4509 4509 4509
Ncbi protein id YP_003024030.1 YP_003024030.1 YP_003024030.1
PhyloP 100V 0.789 0.789 0.789
PhyloP 470Way 0.929 0.929 0.929
PhastCons 100V 0.002 0.002 0.002
PhastCons 470Way 0.009 0.009 0.009
PolyPhen2 possibly_damaging possibly_damaging possibly_damaging
PolyPhen2 score 0.66 0.75 0.66
SIFT neutral neutral neutral
SIFT score 0.64 0.52 0.64
SIFT4G Damaging Damaging Damaging
SIFT4G score 0.005 0.027 0.005
VEST Neutral Neutral Neutral
VEST pvalue 0.54043948 0.5726291 0.54043948
VEST FDR 0.85 0.85 0.85
Mitoclass.1 damaging neutral damaging
SNPDryad Neutral Neutral Neutral
SNPDryad score 0.58 0.61 0.58
MutationTaster . . .
MutationTaster score . . .
MutationTaster converted rankscore . . .
MutationTaster model . . .
MutationTaster AAE . . .
fathmm . . .
fathmm score . . .
fathmm converted rankscore . . .
AlphaMissense likely_benign likely_benign likely_benign
AlphaMissense score 0.1652 0.0681 0.1652
CADD Deleterious Neutral Deleterious
CADD score 2.859355 2.353548 2.995968
CADD phred 21.7 18.52 22.2
PROVEAN Damaging Damaging Damaging
PROVEAN score -2.55 -3.28 -2.55
MutationAssessor . medium .
MutationAssessor score . 2.2 .
EFIN SP Neutral Neutral Neutral
EFIN SP score 0.966 0.998 0.966
EFIN HD Neutral Neutral Neutral
EFIN HD score 0.404 0.684 0.404
MLC Neutral Neutral Neutral
MLC score 0.01551089 0.01551089 0.01551089
PANTHER score . . .
PhD-SNP score . . .
APOGEE1 Neutral Neutral Neutral
APOGEE1 score 0.29 0.39 0.36
APOGEE2 Likely-benign Likely-benign Likely-benign
APOGEE2 score 0.214981566848079 0.0763710639400494 0.214981566848079
CAROL neutral neutral neutral
CAROL score 0.59 0.73 0.59
Condel deleterious neutral deleterious
Condel score 0.49 0.39 0.49
COVEC WMV . . .
COVEC WMV score 0 0 0
MtoolBox deleterious deleterious deleterious
MtoolBox DS 0.43 0.48 0.43
DEOGEN2 . . .
DEOGEN2 score . . .
DEOGEN2 converted rankscore . . .
Meta-SNP . . .
Meta-SNP score . . .
PolyPhen2 transf low impact low impact low impact
PolyPhen2 transf score -1.03 -1.21 -1.03
SIFT_transf medium impact medium impact medium impact
SIFT transf score 0.43 0.31 0.43
MutationAssessor transf medium impact medium impact medium impact
MutationAssessor transf score 1.16 0.62 1.16
CHASM Neutral Neutral Neutral
CHASM pvalue 0.5 0.53 0.5
CHASM FDR 0.85 0.85 0.85
ClinVar id 692847.0 692848.0 .
ClinVar Allele id 681383.0 681384.0 .
ClinVar CLNDISDB MONDO:MONDO:0009723,MedGen:C0023264,OMIM:256000,Orphanet:506 MONDO:MONDO:0009723,MedGen:C0023264,OMIM:256000,Orphanet:506 .
ClinVar CLNDN Leigh_syndrome Leigh_syndrome .
ClinVar CLNSIG Uncertain_significance Uncertain_significance .
MITOMAP Disease Clinical info . Severe mitochondrial disorder .
MITOMAP Disease Status . Reported .
MITOMAP Disease Hom/Het ./. +/- ./.
MITOMAP General GenBank Freq 0.0016% 0.0033% .
MITOMAP General GenBank Seqs 1 2 .
MITOMAP General Curated refs . 20207608 .
MITOMAP Variant Class polymorphism polymorphism;disease .
gnomAD 3.1 AN 56434.0 56432.0 .
gnomAD 3.1 AC Homo 2.0 3.0 .
gnomAD 3.1 AF Hom 3.54396e-05 5.31613e-05 .
gnomAD 3.1 AC Het 0.0 2.0 .
gnomAD 3.1 AF Het 0.0 3.54409e-05 .
gnomAD 3.1 filter PASS PASS .
HelixMTdb AC Hom 16.0 2.0 .
HelixMTdb AF Hom 8.163974e-05 1.0204967e-05 .
HelixMTdb AC Het 1.0 3.0 .
HelixMTdb AF Het 5.1024836e-06 1.530745e-05 .
HelixMTdb mean ARF 0.82387 0.52633 .
HelixMTdb max ARF 0.82387 0.72034 .
ToMMo 54KJPN AC . 3 .
ToMMo 54KJPN AF . 5.5e-05 .
ToMMo 54KJPN AN . 54302 .
COSMIC 90 . . .
dbSNP 156 id . . .
For more info, please check the output legend.
ΔΔG values >±0.61 Kcal/mol are indicative of disrupting variants.
ΔΔG values close to zero (<±0.1 Kcal/mol) are indicative of possibly
compensating double mutants.
For more info, please check the output legend.
ΔΔG values >±0.61 Kcal/mol are indicative of disrupting variants.
ΔΔG values close to zero (<±0.1 Kcal/mol) are indicative of possibly
compensating double mutants.
For more info, please check the output legend.
ΔΔG values >±0.61 Kcal/mol are indicative of disrupting variants.
ΔΔG values close to zero (<±0.1 Kcal/mol) are indicative of possibly
compensating double mutants.
For more info, please check the output legend.
For more info, please check the output legend.
0
Details:
0
Score:  
0
  [min -20, max 10]
  • Predicted accelerated evolution:  score <= 0
  • Conserved:  score > 0
Score:  
0
  [min -20, max 12]
  • Predicted accelerated evolution:  score <= 0
  • Conserved:  score > 0
Score:  
0
  [min 0, max 1]
  • Non-conserved:  score <= 0.7
  • Conserved:  score > 0.7 (soft threshold)
Score:  
0
  [min 0, max 1]
  • Non-conserved:  score <= 0.7
  • Conserved:  score > 0.7 (soft threshold)
Score:  
0
  [min 0, max 1]
  • Neutral:  score <= 0.15
  • Possibly damaging:  0.15 < score <= 0.85
  • Probably damaging:  score > 0.85
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.05
  • Deleterious:  score <= 0.05
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.05
  • Deleterious:  score <= 0.05
Score:  
0
  [min -16.13, max 10.64]
  • Neutral:  score > 1.5
  • Deleterious:  score <= 1.5
Score:  
0
  [min 0.0, max 1.0]
  • Likely benign:  score <= 0.34
  • Ambiguous:  0.34 < score < 0.56
  • Likely pathogenic:  score >= 0.56
Score:  
0
  [min -14, max 14]
  • Neutral:  score > -2.5
  • Deleterious:  score <= -2.5 (soft threshold)
Score:  
0
  [min -6, max 6]
  • Neutral:  score <= 0.8
  • Low impact:  0.8 < score <= 1.9
  • Medium impact:  1.9 < score <= 3.5
  • High impact:  score > 3.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.6
  • Damaging:  score <= 0.6
Score:  
0
  [min 0, max 1]
  • Neutral:  score > 0.28
  • Damaging:  score <= 0.28
Phred score:  
0
  [min 0, max Unlimited]
  • Neutral:  score < 20 (soft threshold)
  • Deleterious:  score >= 20
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5 (soft threshold)
  • Deleterious:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Disease:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Disease:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Polymorphism:  score < 0.5
  • Disease causing:  score >= 0.5
P-value:  
0
  [min 0, max 1]
  • Neutral:  p-value > 0.05
  • Pathogenic:  p-value <= 0.05
Score:  
0
  [min 0, max 1]
No hard-thresholds were indicated by authors (ref). Indicatively:
  • Neutral:  score < 0.9
  • Pathogenic:  score >= 0.9
No score. Categorical only
Please refer to Additional File 14: Table S10 for further details.
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.98
  • Deleterious:  score >= 0.98
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Disease:  score >= 0.5
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Deleterious:  score >= 0.5
Score:  
0
  [min -6, max 6]
  • Neutral:  score < 0
  • Deleterious:  score > 0
  • Inaccurate prediction:  score = 0
Score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.5
  • Deleterious:  score >= 0.5
DS score:  
0
  [min 0, max 1]
  • Neutral:  score < 0.43
  • Deleterious:  score >= 0.43
Pathogenicity score:  
0
  [min 0, max 1]
  • Neutral:  score ≤ 0.5
  • Pathogenic:  score > 0.5


Pathogenicity score for this variant:  
0
  [min 0, max 1]
ACMG-AMP curations for mitochondrial variants should use the raw scores. Standalone probabilities are shown below:
  • Benign:  score ≤ 0.062 (prob. ≤ 0.001)
  • Likely-benign:  0.062 < score ≤ 0.265 (0.001 < prob. ≤ 0.1)
  • Low-scoring VUS (VUS-):  0.265 < score ≤ 0.396 (0.1 < prob. ≤ 0.33)
  • VUS:  0.396 < score ≤ 0.544 (0.33 < prob. ≤ 0.66)
  • High-scoring VUS (VUS+):  0.544 < score < 0.716 (0.66 < prob. < 0.9)
  • Likely-pathogenic:  0.716 ≤ score < 0.907 (0.9 ≤ prob. < 0.99)
  • Pathogenic:  score ≥ 0.907 (prob. ≥ 0.99)
Score:  
0
  [min -5, max 5]
  • Low impact:  score <= -1 (soft threshold)
  • Medium impact:  -1 < score < 1.5 (soft threshold)
  • High impact:  score >= 1.5 (soft threshold)
Score:  
0
  [min -5, max 5]
  • Low impact:  score <= -1
  • Medium impact:  -1 < score < 2 (soft threshold)
  • High impact:  score >= 2 (soft threshold)
Score:  
0
  [min -5, max 5]
  • Low impact:  score <= -1
  • Medium impact:  -1 < score < 2 (soft threshold)
  • High impact:  score >= 2 (soft threshold)
P-value:  
0
  [min 0, max 1]
  • Neutral:  FDR > 0.2
  • Driver:  FDR <= 0.2
The frequency of a CPD variant is proportional to the
number of aligned orthologous sequences that
carry a specific human pathogenic variant as
wild-type amino acid on the total number of aligned
sequences.

For more info, please check the output legend