The AlphaMissense AI model, developed by Google DeepMind in 2023, classifies missense variants, predicting whether they are more likely to be pathogenic or benign. AlphaMissense is based on the AlphaFold 2 AI system, which predicts structures for nearly all proteins known to science from their amino acid sequences.

AlphaMissense analyses related protein sequences and the structural context of variants to estimate how likely a variant is to be pathogenic. AlphaMissense does not predict impact on biophysical properties or specific diseases. Regions of high pathogenicity scores within proteins are also indicative of evolutionary constraint or functional importance.

What is a missense variant?
A missense variant is a genetic alteration in which base pair substitution alters the genetic code to produce an amino acid that is different from the most commonly found amino acid at that position. The average person carries more than 9,000 missense variants. Most are benign and have little to no effect, but others are pathogenic and can severely disrupt protein function