Here we have provided evidence that the 9p21.3 association for risk of ALL can be ascribed to a recurrent rare high impact variant in CDKN2A. CDKN2A encodes both p16 (INK4A), a negative regulator of cyclin-dependant kinases, and p14 (ARF1), an activator of p53. This evidence concerns the gene TP53 and acute lymphoblastic leukemia.