Exceptions to this trend are genes that suffer germline variants that confer susceptibility to cancer, such as the von Hippel-Lindau syndrome caused by some variants in VHL; Cowden disease 5 caused by mutations in PIK3CA; Li-Fraumeni syndrome 1 and TP53; and proteins related to the RAS family, or belonging to RAS pathways, whose germline mutations produce developmental diseases that frequently increase the risk of cancer29. The gene discussed is TP53; the disease is von Hippel-Lindau disease.