In this cohort study, the phenotypes within the classification Li-Fraumeni spectrum were defined, and data from 3034 persons from 1282 families with data available in the International Agency for Research on Cancer TP53 Database were analyzed and classified to reveal meaningful differences in the TP53 variant distribution between patients who met vs those who did not meet Li-Fraumeni syndrome testing criteria. This evidence concerns the gene TP53 and Li-Fraumeni syndrome.