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.
Authors' Recommended Pathogenicity threshold
Misclassified known pathogenic variants
Score a variant
Enter the GRCh37/hg19 coordinate for a missense variant to retrieve its M-CAP score.
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