Figure 1. Functional inference scores across all PharmGKB variants grouped by confidence level.

Distribution of functional effect scores of PharmGKB variants predicted by six mutation effect inference tools. Boxplots shown are of (A) CADD Phred score, (B) PolyPhen2 score, (C) SIFT score, (D) Mutation Assessor score, (E) MutPred score and (F) REVEL score. Scores are plotted for each tool in variant confidence categories (from 1 (highest) to 4 (lowest)) assigned by the PharmGKB annotation. Each tool is annotated with the information types it employs to make predictions—Seq: sequence conservation, Struct: protein structural metrics, Ens: an ensemble tool that integrates results of several individual tools. Each tool employs categorical cutoffs with the most damaging category colored as red.