Within the coding region of a gene, we identify nonsense SNPs that lead to premature termination of translation and are therefore very likely to affect protein function. In addition, non-synonymous polymorphisms (nsSNPs) that lead to amino acid changes may also affect protein function depending on the location and nature of the amino acid substitution. We used two in silico classification programs, Polyphen (8) and SNPs3D (9), to predict the effect of an amino acid substitution on the structure and function of a human protein, and then classified nsSNPs as possibly or probably damaging or benign.
