We calculated a Bonferroni corrected p-value for the null hypothesis of no deviation from the expected frequency of two variants in the same gene in three out of three unrelated, affected individuals over the ~17,000 genes in CCDS2008. Assuming all genes are of the same length and have the same mutation rate, the rate of novel NS/SS/I variants per gene was 0.0309 (i.e., ~526 novel NS/SS/I variants per 17,000 genes). If the variants occur independently of one another, two variants occur in the same gene at a rate of (0.0309)2 or 9.57 × 10-4 so the p-value is ((9.57 × 10-4)3 × 17,000) or ~0.000015. Hence, even after correcting for searching across all genes, the result remains highly significant.
