In an epidemiologic analysis of known and predicted loss‐of‐function variants in POMC, PCSK1, and LEPR, the number of individuals in the United States who had MC4R pathway diseases associated with obesity was estimated to be 12,800 out of a total population of 300 million (0.004%), most of whom remain undiagnosed [21]. Here, MC4R is linked to obesity due to melanocortin 4 receptor deficiency.