MHPA analysis led to the discovery that UV-induced mutations causing inactivation of TSC2 are pervasive in facial skin of individuals with TSC, generating hundreds of thousands of fibroblast proliferations and incipient facial tumors (subclinical “micro-FAFs”) due to second-hit mutations in TSC2, a small proportion of which develop into observable FAF lesions. Here, TSC2 is linked to tuberous sclerosis.