CADD

From the abstract of the paper:

Combined Annotation-Dependent Depletion (CADD) is a method for objectively integrating many diverse annotations into a single measure (C score) for each variant. CADD was implemented as a support vector machine trained to differentiate 14.7 million high-frequency human-derived alleles from 14.7 million simulated variants. C scores correlate with allelic diversity, annotations of functionality, pathogenicity, disease severity, experimentally measured regulatory effects and complex trait associations, and they highly rank known pathogenic variants within individual genomes.