The burden of LoF variants in ASXL1 and AlphaMissense variants in DNMT3A, SF3B1, PTEN, TP53 and SRSF2 were strongly linked to an increased risk of leukemia: acute myeloid leukemia (ASXL1: Odds Ratio (OR)=1.05; p=8.6× 10−170; DNMT3A: OR=1.03 , p=2.1× 10−150; SRSF2: OR=1.3 , p=1.2× 10−195; TP53: OR=1.05, p=4.7× 10−35), monocytic leukemia (DNMT3A: OR=1.01, p=2.5 × 10−9), chronic lymphoid leukemia (SF3B1: OR=1.07, p=4.1× 10−68) and acute lymphoid leukemia (PTEN: OR=1.01, p =2.1 × 10−14 ). The gene discussed is ASXL1; the disease is acute lymphoblastic leukemia.