Mendelian Clinically Applicable Pathogenicity (M-CAP) Score

M-CAP is the first pathogenicity classifier for rare missense variants in the human genome that is tuned to the high sensitivity required in the clinic (see Table). By combining previous pathogenicity scores (including SIFT, Polyphen-2 and CADD) with novel features and a powerful model, we attain the best classifier at all thresholds, reducing a typical exome/genome rare (<1%) missense variant (VUS) list from 300 to 120, while never mistaking 95% of known pathogenic variants as benign. Further details can be found here.

Method Authors' Recommended Pathogenicity threshold Misclassified known pathogenic variants
SIFT < 0.05 38%
Polyphen-2 > 0.8 31%
CADD > 20 26%
MetaLR > 0.5 27%
M-CAP > 0.025 5%

Score a variant

Enter the GRCh37/hg19 coordinate for a missense variant to retrieve its M-CAP score.

GRCh37/hg19

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GRCh37/hg19.{{chrom}}:{{pos | number}} Reference Allele {{ref}}

Alt M-CAP 95% TPR
{{allele.alt}} {{allele.mcap | number:3}} Likely Benign Possibly Pathogenic
M-CAP scores not available for some alleles at {{chrom}}:{{pos | number}}.
M-CAP scores only rare (≤ 1% allele frequency), missense variants based on the Ensembl build 75 gene set.
No M-CAP scores available for {{chrom}}:{{pos | number}}.
M-CAP scores only rare (≤ 1% allele frequency), missense variants based on the Ensembl build 75 gene set.

How to cite

Jagadeesh, K., Wenger, A., Berger, M., Guturu, H., Stenson, P., Cooper, D., Bernstein, J., and Bejerano, G. (2016). M-CAP eliminates a majority of variants with uncertain significance in clinical exomes at high sensitivity. Nature Genetics, 2016. DOI: 10.1038/ng.3703

Download M-CAP Scores

M-CAP source code

M-CAP public git repository can be found here.

Licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. Please email for commercial licensing inquiries.