MC4R rs61992485: What Your Genotype Means
The genetic variant rs61992485 is an extremely rare missense alteration situated within the melanocortin-4 receptor (MC4R) gene. This gene produces a critical brain receptor responsible for regulating appetite, satiety, and systemic energy balance. Research has evaluated rs61992485 for potential effects on receptor signaling and susceptibility to altered body mass index, although current clinical evidence regarding its precise impact remains limited.
What each genotype means
Typical MC4R genotype
This is the most common genotype for this location in the MC4R gene. It is considered the baseline or reference state in most populations, and there is no evidence suggesting this specific genotype contributes to altered MC4R function or obesity risk.
This is the predominant genotype found in the vast majority of individuals across all global populations.
Rare variant carrier
This genotype indicates you carry one copy of the rare T allele at this position. Because rs61992485 is an extremely rare variant, its specific functional impact on the melanocortin-4 receptor and its association with body weight or energy homeostasis remains limited and not fully established in clinical research. You should not assume this result has a direct impact on your health, as rare variants often require further study to determine their clinical significance.
This genotype is extremely rare, with an allele frequency of less than 0.001 in general population databases like gnomAD.
Rare variant homozygous
This genotype indicates you carry two copies of the rare T allele. Given the extreme rarity of this variant, there is currently insufficient published evidence to characterize the specific phenotypic consequences or health implications of being homozygous for this change. Clinical interpretation of such rare genotypes is limited, and it should not be used to infer personal health risks without professional medical consultation.
This genotype is exceptionally rare and is not expected to be observed in most population samples.
Understanding rs61992485 and the MC4R Locus
The single nucleotide polymorphism rs61992485 is a coding missense variation located on chromosome 18 inside the melanocortin-4 receptor (MC4R) gene. In genetics, a missense variant alters a single DNA nucleotide within an exon, resulting in the substitution of one amino acid for another in the translated protein chain. Because MC4R is a single-exon G protein-coupled receptor spanning transmembrane domains, any change to its amino acid sequence can alter structural stability or surface localization. Public genomic repositories like dbSNP and Ensembl catalog rs61992485 as an extremely low-frequency coding change. While many synonymous variants leave the resulting protein structure unaltered, missense variants like rs61992485 are prioritized by researchers to evaluate whether the physical conformation or signaling ability of the receptor is shifted.
The Biological Function of the MC4R Pathway
The MC4R gene produces a central nervous system receptor primarily expressed in the paraventricular nucleus of the hypothalamus. This receptor acts as a major control hub in the leptin-melanocortin pathway, which governs hunger, food intake, and resting metabolic expenditure. When alpha-melanocyte-stimulating hormone (alpha-MSH) binds to MC4R, it triggers intracellular signaling pathways—such as cyclic AMP production and beta-arrestin recruitment—that signal satiety to the brain, suppressing appetite. Complete disruption or loss of MC4R function represents the single most common monogenic cause of severe early-onset obesity. Conversely, variants that retain normal function or enhance receptor signaling bias can protect individuals from metabolic strain. Therefore, any genetic variation within the MC4R coding sequence attracts considerable scientific focus.
Current Scientific Evidence and Obesity Susceptibility
Research examining coding variations in MC4R has demonstrated that alterations can lead to loss-of-function, neutral signaling, or even gain-of-function phenotypes. Large population cohort studies, such as analyses of the UK Biobank, have systematically genotyped and functionally tested tens of naturally occurring nonsynonymous MC4R variants to observe their relationship with body mass index (BMI) and cardiometabolic traits. However, rs61992485 is an ultra-rare variant, and evidence specifically connecting it to clinical phenotypes is categorized as limited. Because it appears in so few individuals worldwide, large-scale genome-wide association studies (GWAS) often lack statistical power to definitively quantify its independent effect size. Computational modeling and in vitro cellular assays are required to determine whether it alters ligand binding, but clinical assertions must be interpreted with caution.
Population Distribution and Rarity
According to data from the Genome Aggregation Database (gnomAD) and international sequencing projects, rs61992485 is exceptionally rare across all surveyed human ancestries. The global minor allele frequency is well below 0.001 (less than 0.1%), meaning that the vast majority of the global population carries the homozygous reference genotype. In many continental subpopulations, the variant allele is completely absent from sampled reference cohorts. Because extremely rare variants show variable distribution across ancestries due to founder effects or genetic drift, the presence of the alternative allele is sporadic. When interpreting genomic tests, geneticists rely heavily on population databases like gnomAD to distinguish between common, benign polymorphisms and rare variants that require closer biological investigation.
Interpreting Results: What You Can and Cannot Do
Finding an ultra-rare variant in a personal genomic test can easily lead to overinterpretation. Carrying a variant of limited evidence like rs61992485 is not a medical diagnosis of monogenic obesity, nor is it a guarantee of weight dysregulation. Body weight and metabolic health are complex polygenic traits governed by hundreds of common genetic variants interacting with diet, physical activity, sleep, and environmental factors. Furthermore, direct-to-consumer genotyping platforms carry higher false-positive rates for ultra-rare variants than for common SNPs. Consumers should never adjust prescribed medications, dietary regimens, or medical care based on this variant alone. Anyone concerned about familial patterns of severe obesity or metabolic disorders should seek guidance from a licensed genetic counselor or medical provider.
How common is this variant?
The rs61992485 variant is exceptionally rare across worldwide populations, exhibiting a minor allele frequency of less than 0.001 in the gnomAD database, with the vast majority of individuals being homozygous for the reference allele.
Frequently asked questions
Does carrying rs61992485 mean I will develop severe obesity?
No. The presence of a rare variant like rs61992485 is not a clinical diagnosis and does not dictate your body weight. Body composition is shaped by polygenic background alongside nutrition, physical activity, and environment.
What does the MC4R gene do in the body?
The MC4R gene provides instructions for creating the melanocortin-4 receptor, a protein primarily active in the hypothalamus. It plays an essential role in energy balance by receiving hormonal signals that suppress appetite and regulate metabolic energy expenditure.
Why is the evidence for rs61992485 classified as limited?
Because the variant is exceedingly rare in the general population, very few individuals have been identified and studied in scientific literature. Without extensive functional assays and large clinical cohorts, researchers cannot definitively establish its specific impact on receptor activity.
Should I change my diet or lifestyle if I have this variant?
No specific lifestyle adjustments are clinically indicated solely based on this variant. Standard evidence-based practices regarding balanced nutrition and regular physical activity remain the foundation of metabolic health.
Could a direct-to-consumer genetic test report this variant incorrectly?
Yes. Microarray-based direct-to-consumer tests have a relatively high rate of false positives when detecting ultra-rare variants compared to common SNPs. Any unexpected finding in a rare disease gene should be validated through clinical Sanger sequencing.
Sources & further reading
Educational information only, last refreshed 9/7/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs61992485?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29Related variants in MC4R
This variant is a well-replicated risk factor for increased BMI and obesity, influencing appetite regulation.
This variant in the MC4R gene is associated with variations in body mass index (BMI) and obesity risk.
This SNP is a well-known genetic marker associated with body mass index and obesity risk.
This variant near the MC4R gene is associated with increased risk of obesity and altered response to dietary interventions.