a, Schematic illustrating the genomic target (consisting of spacer and adjacent PAM element), RNA guide, and target variation. b, Fraction of residues for individual nucleotides containing variation in the ExAC dataset. c, Fraction of 2-nt PAM motifs altered by variants in the ExAC dataset. d, Percent of target variants at different allele frequencies for each CRISPR endonuclease. e, Cumulative percent of targets containing variants for each CRISPR endonuclease. f, Fraction of targets containing homozygous variants at different allele frequencies. The Mean and SEM for 5 CRISPR endonucleases is shown.