Li-Fraumeni Syndrome (LFS) is a severe cancer predisposition syndrome caused by germline TP53 variants and characterized by a wide range of cancers. The TP53 variant p.R181H is enriched in the Swedish germline TP53 cohort and has distinct phenotypical characteristics. Using our nationwide Swedish germline TP53 database (SWEP53, 189 individuals, 86 families), p.R181H was identified in 22% of families (19/86), compared to just 0.6% in the National Cancer Institute (NCI) TP53 database (8/1360). Notably, p.R181H carriers had lower cancer incidence and better survival than carriers of other TP53 variants (both p