AlphaMissense community resource

  • 71 million missense variant predictions covering the human proteome - missense proteome data

  • For each UniProt canonical isoform, first generate all possible SNVs and then keep SNVs that change the protein seq

  • Gene-level AlphaMissense pathogenicity predictions

    • which is the average pathogenicity of all possible missense variants in a gene

    • 216 million possible single amino acid substitutions across 19,233 human proteins (UniProt canonical isoforms)

Important

Missense proteome data :tada:

  • Out of 71 million missense variant covering the human proteome

    • Likely pathogenic: 32% (22.8 million) are and

    • Likely benign: 57% (40.9 million)

  • Classification cutoff: 90% precision using the ClinVar dataset

Applications

  • AlphaMissense findings coupled with donstream functional experiments improve the current understanding of clinically actionable genes and variants

  • Expedite understanding of the molecular effects of variants on protein function.

  • Prioritise rare disease relevant variants

  • Improve the diagnostic yield of rare genetic diseases