Comparisons of the frequency of natural variation in USP9X alleles derived from control individuals in the EXAC database and cancer samples deposited in the COSMIC database (using the most conservative approach where all samples are assumed male to derive USP9X allelic frequencies) reveal that cancer samples have 29 times more synonymous variation, but have 578 times more non-synonymous changes (missense, non-sense and insertion/deletions). The gene discussed is USP9X; the disease is cancer.