Unexplained kidney failure (uKF) accounts for up to 15% of patients who require kidney replacement therapy.1 uKF complicates clinical management because it hinders precise prognosis, may miss opportunities for precision management, and makes transplant counseling unclear for the recipient and potential donors. The discovery of hundreds of monogenic kidney disease genes and risk alleles creates the opportunity to use genetic sequencing to explain why some patients developed uKF. Indeed, previous sequencing studies of uKF have reported a definitive monogenic cause in 12%-50% of cases, with this wide range likely reflecting the heterogeneity of case definition and the number of genes analyzed.