While it is difficult to provide “universal” MAF thresholds, the ACMG does recommend using MAF data as a key filter in their guidelines for variant interpretation. We deem a MAF ≥ 0.5% to be incompatible with a classification of P/LP for hereditary hearing loss aside from specific cases such as variants in GJB2 and SLC26A4, and we use this threshold to automatically classify any variant as B (Table S2).16 It is important to note that with the availability of new datasets from large-population sequencing projects such as gnomAD, MAF for some variants will change, which in turn may affect their clinical significance. While using a universal MAF cutoff is beneficial, for a common disease such as deafness this filter aided in classifying only 4% of coding variants as benign, illustrating that MAF cutoffs and rarity alone are not sufficient to determine deleteriousness.