Rare high-risk pathogenic variants in mismatch-repair genes, PTEN, and DNA polymerase genes4 explain a small proportion of endometrial cancers, and the eight previously published common endometrial cancer-associated single-nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) studies5–8 together explain <5% of the familial relative risk (FRR). The gene discussed is PTEN; the disease is endometrial cancer.