MAF Thresholds for Disease-Causing Variants Are Type Specific
To determine whether MAFs for P+LP variants were mutation-type dependent, we subdivided all variants by effect and plotted against their MAF. Although the median MAF is 0 for all variant types, synonymous and UTR variants had the highest mean MAF (0.023% and 0.027%, respectively), followed by missense (0.017%), nonsense (0.009%), splice-site (0.0047%), in-frame indels (0.0036%), and frameshift indels (0.0028%) (Figure 6C, Table S7). These results compare closely to the gene-level results and demonstrate that regardless of type and gene, disease-causing mutations are ultra-rare and are heavily comprised of novel/private variants.