Obesity has become a great health issue and socioeconomic burden globally in the past few decades and has afflicted Pakistan in the same way. However, there is limited research on obesity genetics in Pakistan. Proopiomelanocortin (POMC) neurons bear leptin receptor and act as anorectic targets of leptin in the brain. Leptin binding induces a series of processing events producing melanocortins which then bind to their respective signals. R236G is a mutation which disrupts such a normal processing event resulting in an overall weight gain and early onset obesity. A total of 475 subjects were genotyped to search for this mutation, and their serum traits were measured. We detected one obese subject heterozygous for R236G (0.4%) and no control subject with the mutation. We then systematically searched for previous reports of R236 substitution and combined the results of our study with the previous frequencies and found that the mutation has an overall prevalence of 0.704% in obese cases and 0.18% in non-obese controls. In conclusion, such mutations involving a prohormone processing site are very rare in nature and may not contribute a significant proportion of common forms of obesity observed currently. Such mutations may exert their effect by affecting other pathways and are more prominent in the early stages of life only.