Most autosomal recessive diseases are rare, but they collectively account for a substantial proportion of disease burden, especially in consanguineous populations. Estimation of this disease burden, however, is hampered by many factors, including lack of countrywide registries. Establishing carrier frequency can be a practical surrogate to estimate disease burden, although the requirement of a large representative cohort may be challenging. We propose that the application of clinical genomics in the diagnostic setting offers a unique opportunity to estimate carrier frequency in the population as a secondary benefit. We used a data set of ~7,100 patients who underwent genomic testing for various Mendelian disorders to estimate the carrier frequency. We were able to calculate the frequency of 259 confirmed founder recessive mutations. We found the corresponding disease burden to be, at minimum, ~7 per 1,000 children born to first-cousin parents, with disorders related to intellectual disability and vision impairment being the most common. Our approach can be utilized to inform the design of new policies for the prevention of genetic disorders and highlights an important secondary benefit of clinical genomics. Genet Med18 12, 1244–1249.