More common, but still quite rare (minor allele frequency (MAF) <5% in most populations) MC4R non-synonymous SNPs (nsSNPs) (rs2229616/Val103Ile and rs52820871/Ile251Leu) have been reproducibly associated with a protective effect from severe and common forms of obesity [11], [12], [13], [14], [15], [16]. The gene discussed is MC4R; the disease is obesity disorder.