Distributions of predicted effect on function for amino acid variants arising from nsSNPs at low (<5%), medium (5–15%), and high (>15%) minor allele frequency in the human population. Prediction confidence is measured by group rank offset (Fig. 4) from the cutoff, where offsets of zero (0) and above are variants predicted to affect function (highest confidence in right-most bin), and offsets below zero are variants predicted to be functionally tolerated (highest confidence in leftmost bin). The data from Cargill et al. (21) and Halushka et al. (22) are represented by the dark and light bars, respectively. Sequences related to each query were taken from Swiss-Prot, and subalignments were determined as described in Methods.