Among the nonpolymorphic RUNX1 variants identified in 430 adult AML specimens from the Leucegene AML cohort, 29% were germline. Of the 10 distinct germline variants identified, 6 were classified as pathogenic or likely pathogenic by the MM VCEP criteria; 8 of the 10 were predicted to be deleterious to RUNX1 function by functional studies or prediction algorithms. VUS, variant of unknown significance.