Nonsynonymous single nucleotide polymorphisms (nsSNPs) lead to amino acid substitutions (AASs) and have the potential to affect the function of the protein product of a gene via the structure, biochemistry and/or splicing of the protein. Advances in high-throughput sequencing technologies have accelerated the rate at which nsSNPs are now being identified [The 1000 Genomes Project, 2010]. Accurate automated computational methods capable of predicting the effects of AASs and amenable to high-throughput analyses of large datasets are therefore of increasing importance for identifying and prioritizing functional nsSNPs for further studies [Thusberg and Vihinen, 2009].
