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.
3/25/2019: M-CAP score file with an interpretable sensitivity score can be found here! Sensitivity score ≤ 0.95 is possibly pathogenic.
| Method | Authors' Recommended Pathogenicity threshold | Misclassified known pathogenic variants |
|---|---|---|
| SIFT | < 0.05 | 38% |
| > 0.8 | 31% | |
| CADD | > 20 | 26% |
| MetaLR | > 0.5 | 27% |
| > 0.025 | 5% |
Score a variant
Enter the GRCh37/hg19 coordinate for a missense variant to retrieve its
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GRCh37/hg19.{{chrom}}:{{pos | number}} Reference Allele {{ref}}
| {{allele.alt}} | {{allele.mcap | number:3}} | Likely Benign Possibly Pathogenic |
No M-CAP scores available for {{chrom}}:{{pos | number}}.
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. 48 (12) 1581 DOI: 10.1038/ng.3703
Download M-CAP Scores
M-CAP only scores rare missense variants: hg19, ENSEMBL 75 missense, ExAC v0.3 where no super population has minor allele frequency above 1%. If a missense variant has no M-CAP score, the M-CAP prediction should be assumed to be likely benign.
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M-CAP v1.0 scores 10/24/2016please do not use -
M-CAP v1.3 raw scores 10/30/2018 -
M-CAP v1.4 raw and normalized scores 3/25/2019 (v1.3 raw score of 0.025 converted to sensitivity score 0.95, to facilitate interpretation)
M-CAP source code
M-CAP public git repository can be found here.
M-CAP train and test data can be found here.
Licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. Please email 
for commercial licensing inquiries.