In addition to GenePipe, there are a number of other web tools such as F-SNP (44), FastSNP (45), Panther (46), PolyPhen2 (9–10), SIFT (39) and SNPs3D (47) which assess the biological relevance of a SNP independently of genotype–phenotype correlation results (Table 1). Half of the eight tools shown in Table 1 deal exclusively with non-synonymous SNPs. Of the remaining four, only SPOT and FastSNP attempt to combine evidence from multiple sources of information and return a single measure of biological relevance suitable for systematically prioritizing GWAS results. FastSNP, while providing a great deal of information in very informative diagrammatic format, does not account for LD proxies. The evidence that the tools in Table 1 can be used to predict causal variants that influence general common complex disease, subject to the aforementioned validation criteria for causal variants, is limited. PolyPhen (10) and SIFT (39), which deal exclusively with non-synonymous SNPs, have found evidence of prediction using information on disease-related variants from the UniProt database (60) for Mendelian disorders flagged by terms such as ‘lethal’ and ‘complete loss of function’ (PolyPhen is
