Fig. 6.

Stability effects of nonsynonymous SNPs segregating at various allelic frequencies. (A) λ is the maximum frequency that a segregating SNP attains over its lifetime. Selection shifts the distribution of higher frequency alleles toward more stabilizing SNPs. (B) ΔΔG of SNPs in the coding region of the human genome estimated using FoldX (Schymkowitz et al. 2005) and compiled by the database SNPeffect (De Baets et al. 2012) (see Materials and Methods). Allele frequency is taken from dBSNP. For arising ΔΔG, we use the empirically measured ΔΔG from a diverse set of proteins in the ProTherm database (Kumar et al. 2006; Tokuriki et al. 2007). Enclosed in parentheses are the number of SNPs for the indicated frequency cutoff.