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durable outcomes.As whole-genome data become available for increasing numbers of individuals across diverse populations, the list of genomic variants of unknown significance (VOUS) continues to grow. One powerful tool in VOUS interpretation is determining whether an allele is too common to be considered pathogenic. As genetic and epidemiological parameters vary across disease models, so too does the pathogenic allele frequency threshold for each disease gene. One threshold-setting approach is the maximum credible allele frequency (MCAF)