In the present study, we perform an exome-focused GWAS to systematically examine the impact of germline-coding variants on the development of ALL in children of European descent, experimentally explore the functional consequences of the genome-wide significant variant in the CDKN2A gene, and comprehensively characterize coding variation at this locus by targeted resequencing. This evidence concerns the gene CDKN2A and acute lymphoblastic leukemia.