Polyphen, now available in its version Polyphen2, predicts the impact of a missense mutation based on (1) protein sequence (2) phylogenetic information and (3) structural information. The software actually looks if the mutation is falling within a protein domain essential for the binding to other molecules of for the formation of the secondary/tertiary structure. In particularly Polyphen2 looks at putative disulfide bonds, active sites, binding sites and transmembrane domains and makes computations on 3D models of the protein structure. Polyphen2 also looks at homologous proteins to see if the identified missense mutation has been observed in other proteins of the same family.
