PolyPhen-2 is an automatic tool for prediction of the possible impact of an amino acid substitution on the structure and function of a human protein. Automated predictions of this kind are essential for interpreting large datasets of rare genetic variants, which have many applications in modern human genetics research. Uses in recent research include identifying rare alleles that cause Mendelian disease, scanning for potentially medically actionable alleles in an individual’s genome, and profiling the spectrum of rare variation uncovered by deep sequencing of large populations.
