Holly Tabor, Michael Bamshad and colleagues searched for pathogenic variants in the high-coverage exome sequences of 4,313 European-American and 2,204 African-American individuals from over 20 cohorts within the National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (Am. J. Hum. Genet. doi:10.1016/j.ajhg.2014.07.006; 31 July 2014). They focused on variants in 39 genes for 31 mendelian disorders, 17 genes associated with age-related macular degeneration (AMD) and 14 genes implicated in drug response. In total, they identified 10,879 variants in these 70 disease-related genes and validated 399 risk variants, including 328 for mendelian disorders, 25 for AMD and 46 for drug response. The mean number of risk alleles per individual in the combined data set was estimated to be 15.3, with 0.57 for mendelian disorders, 3.16 for AMD and 11.5 for drug response. They found that 45% of individuals had at least one pathogenic allele for mendelian disorders and over 99.98% of individuals carried one or more risk alleles for AMD. Each individual also carried at least five functional alleles in genes associated with drug response. The carrier burden for severe recessive childhood disorders was estimated to be 0.57, significantly lower than previously reported estimates. This study highlights the striking prevalence of actionable incidental or secondary results, including ones of direct clinical usefulness, which might be obtained in patient sequencing.