PolyPhen-2 (Polymorphism Phenotyping v2) is a software tool which predicts possible impact of amino acid substitutions on the structure and function of human proteins using straightforward physical and evolutionary comparative considerations.

Explore navigation menu on the left to find out more About PolyPhen-2, consult the Documentation (work in progress), or Download standalone software, datasets and publications.

You can also Query PolyPhen-2 web server, including bulk submission in Batch query mode.

Precomputed set of whole human exome sequence space (WHESS) PolyPhen-2 annotations is also available, comprising ~150,000,000 putative single-nucleotide non-synonymous (missense) codon changes enumerated for each CDS codon position in the exons of 43,043 UCSC knownGene human transcripts (hg19/GRCh37). PolyPhen-2 predictions were calculated for all resulting amino acid residue substitutions in human UniProtKB proteins with the maximum CDS sequence overlap and identity.

Visit PolyPhen-2 WHESS.db page to search the database of WHESS annotations.