====== PolyPhen-2 ====== **PolyPhen-2** (**Poly**morphism **Phen**otyping v**2**) 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|About]] PolyPhen-2, consult the [[docs|Documentation]] (work in progress), or [[downloads|Download]] standalone software, datasets and publications. You can also [[http://genetics.bwh.harvard.edu/pph2/|Query]] PolyPhen-2 web server, including bulk submission in [[http://genetics.bwh.harvard.edu/pph2/bgi.shtml|Batch query]] mode. Precomputed set of whole human exome sequence space ([[downloads#datasets|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 [[http://genetics.bwh.harvard.edu/pph2/dbsearch.shtml|WHESS.db]] page to search the database of WHESS annotations.