Inferring the molecular and phenotypic impact of amino acid variants with MutPred2

Identifying pathogenic variants and underlying functional alterations is challenging. To this end, we introduce MutPred2, a tool that improves the prioritization of pathogenic amino acid substitutions over existing methods, generates molecular mechanisms potentially causative of disease, and returns interpretable pathogenicity score distributions on individual genomes. Whilst its prioritization performance is state-of-the-art, a distinguishing feature of MutPred2 is the probabilistic modeling of variant impact on specific aspects of protein structure and function that can serve to guide experimental studies of phenotype-altering variants. We demonstrate the utility of MutPred2 in the identification of the…

• AP
  Alfred P. Sloan Foundation
• SF
  Simons Foundation

  Award: 345469
• GA
  Gordon and Betty Moore Foundation
• WR
  Washington Research Foundation
• NI
  National Institutes of Health

  Awards: MH104766, MH105524, MH109885, R01 MH105524, R01 LM009722, LM009722, R01 MH109885
• NI
  National Institute of Mental Health

  Awards: R01 MH109885, R01 MH105524, R01 MH076431, R01 MH104766
• UN
  U.S. National Library of Medicine

  Awards: R01 LM009722, K99 LM012992