The human serotonin 2C (5-HT2C) receptor undergoes extensive RNA editing, generating multiple isoforms; the most prominent isoform in the human brain is the extensively edited VSV isoform. In addition, a naturally occurring single nucleotide polymorphism (SNP) is found in the coding region of the 5-HT2C receptor gene, which converts cysteine to serine at the 23rd amino acid (C23S). To elucidate the functional consequences, pharmacological properties were evaluated in cells expressing C23 or S23 in the nonedited, INI, or edited, VSV, isoform. Confocal imaging of HEK293 cells expressing the C23 and S23 variants revealed no apparent difference in cellular localization, which was confirmed in NIH-3T3 fibroblasts by surface biotinylation. Competition binding experiments revealed comparable high-affinity agonist binding for the C23 and S23 receptors and no difference in ligand affinities in either the INI or VSV backbones. The dose-response functions for 5-HT and (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (DOI) to elicit phosphoinositide hydrolysis did not differ in either HEK293 or NIH-3T3 fibroblasts expressing the receptor variants. Constitutive activity, evaluated in COS-7 and HEK293 cells, also was not different. Lastly, fluorescence resonance energy transfer demonstrated homodimerization of C23 receptors, which was reproduced in cells expressing the S23 variant. We conclude that the C23S SNP in the 5-HT2C receptor has no functional consequences, even when evaluated in the most common, edited receptor backbone. Therefore, positive associations between this polymorphism and disease states may be a consequence of linkage disequilibrium with another SNP that is involved in the disease.