SLC45A2 rs16891983: What Your Genotype Means
The rs16891983 variant is a specific genetic change located within the SLC45A2 gene. It is widely recognized as an ancestry-informative marker strongly associated with variations in human skin, hair, and eye pigmentation.
What each genotype means
Typical light pigmentation
You carry two copies of the derived G allele (encoding leucine at codon 374, often designated 374Leu). In genome-wide association studies, this genotype is strongly associated with lighter skin, lighter hair, and lighter eye pigmentation typical of European ancestry, as well as reduced melanin synthesis. Because lighter pigmentation provides less natural UV shielding, it is also statistically linked to an increased baseline vulnerability to sunburn and melanoma compared to darker-pigmented genotypes.
Carried by more than 90% of individuals of Northern and Western European ancestry, but rare in African and East Asian populations.
Intermediate pigmentation tendency
You carry one ancestral C allele (374Phe) and one derived G allele (374Leu). This heterozygous genotype is associated with intermediate pigmentation traits, often resulting in darker hair, eyes, or skin compared to individuals homozygous for the G allele. Published studies note that having at least one C allele correlates with a reduced risk of cutaneous melanoma relative to the GG genotype, largely mediated through increased melanin production.
Found in approximately 5% to 15% of Southern European and admixed populations, but uncommon in individuals of unadmixed Northern European or East Asian descent.
Typical darker pigmentation
You carry two copies of the ancestral C allele (encoding phenylalanine at codon 374, designated 374Phe). In genetic association research, this genotype is strongly associated with darker skin, hair, and eye pigmentation, as well as darker hair color even within European cohorts. Due to higher natural eumelanin levels, individuals with this genotype statistically exhibit greater natural UV photoprotection and lower baseline odds of melanoma relative to carriers of the derived G allele.
Present in nearly 98% to 100% of individuals of African, East Asian, and Indigenous American ancestries, while being exceedingly rare (less than 1%) in Northern Europeans.
Understanding the Variant
The rs16891983 variant is a single nucleotide polymorphism (SNP) located in the SLC45A2 gene, which encodes a membrane-associated transporter protein. This specific variant is often referred to as the p.Phe374Leu mutation, representing a change in the amino acid sequence of the protein. Because of its location and functional impact, it serves as a classic signature of recent positive selection in human populations. Researchers study this variant to understand how human pigmentation has evolved across different geographic regions. It is not a disease-causing mutation in the traditional sense, but rather a functional polymorphism that contributes to the wide spectrum of normal human physical traits. By analyzing this site, scientists can trace historical migration patterns and the selective pressures that shaped human appearance over thousands of years.
The Role of SLC45A2
The SLC45A2 gene plays a critical role in the melanin biosynthetic process. The protein it produces is essential for the proper function of melanosomes, the specialized organelles within cells where pigment is produced and stored. By regulating the pH within these melanosomes, the SLC45A2 protein influences the type and amount of melanin synthesized by melanocytes. When this gene functions normally, it helps determine the natural color of an individual's skin, hair, and eyes. Disruptions or variations in this gene are linked to both normal pigment variation and, in rare cases, inherited conditions such as oculocutaneous albinism type 4. Because it is central to the production of melanin, it is a primary focus for researchers investigating the biological pathways that connect pigmentation to other health outcomes, including the development of skin cancers.
Research and Associations
Scientific research has consistently identified rs16891983 as a significant factor in pigmentation studies. Large-scale genome-wide association studies (GWAS) have linked this variant to skin color, hair color, and eye color across diverse populations. Beyond physical appearance, the variant has been studied for its potential role in melanoma risk. Some studies suggest that certain alleles of this gene may have an additive effect on melanoma susceptibility, often interacting with other pigmentation genes like MC1R. However, the evidence regarding its direct role in cancer risk is considered limited and complex, as it is often tied to the underlying pigmentation phenotype rather than being an independent driver of malignancy. It is important to note that these associations are statistical in nature and do not imply a direct cause-and-effect relationship for any individual's health status.
Population Frequency
The distribution of the rs16891983 alleles varies significantly across global populations, reflecting historical selective pressures. The Leu374 allele is found at high frequencies or is near-fixed in many African populations. In contrast, the Phe374 allele has been subject to positive selection in European populations, leading to its higher prevalence in those groups. This divergence is a hallmark of human adaptation to different environmental conditions, particularly varying levels of ultraviolet radiation. Because these frequencies are so distinct, the variant is frequently used by geneticists as an ancestry-informative marker. Understanding these population-specific patterns is essential for interpreting genetic data accurately, as the significance of a particular genotype can depend heavily on an individual's ancestral background.
What This Information Means for You
Knowing your genotype for rs16891983 provides insight into your genetic predisposition for certain physical traits, such as skin or hair color. However, it is important to recognize that this information is primarily educational and reflects statistical trends observed in large groups of people. It cannot be used to diagnose any medical condition or predict your personal risk for skin cancer. If you have concerns about your skin health, such as changes in moles or skin lesions, you should consult a dermatologist for a professional evaluation. Genetic variants are only one piece of a much larger puzzle that includes environmental factors, lifestyle, and other genetic influences. Always discuss any health-related genetic findings with a qualified healthcare provider who can help you interpret the results in the context of your overall medical history.
How common is this variant?
The Leu374 allele is fixed or near-fixed in African populations, while the Phe374 allele is more common in European populations due to historical positive selection.
Frequently asked questions
Is rs16891983 a cause of melanoma?
No, rs16891983 is not a direct cause of melanoma. While some studies have found statistical associations between this variant and melanoma risk, it is likely linked to the underlying pigmentation phenotype rather than being a direct driver of cancer.
Can I use this genotype to predict my skin color?
While this variant is associated with skin pigmentation, it is only one of many genetic factors that determine your physical appearance. It cannot be used to accurately predict your skin color, as many other genes and environmental factors are involved.
Should I be worried if I have the Phe374 allele?
No, there is no reason for concern. This variant is a common genetic polymorphism associated with normal human variation in pigmentation and is not a disease-causing mutation.
How do I find out my genotype for this variant?
Your genotype for this variant may be included in reports from direct-to-consumer genetic testing services. If you are interested in your genetic makeup, you can discuss the utility of such testing with a genetic counselor or your primary care physician.
Sources & further reading
Educational information only, last refreshed 10/11/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This synonymous variant is in high linkage disequilibrium with functional alleles that influence human skin, hair, and eye pigmentation.
This missense variant (p.Phe374Leu) is a major determinant of human skin, hair, and eye pigmentation, showing strong evidence of selection in European populations.
Synonymous marker in the SLC45A2 locus associated with skin reflectance, tanning response, and freckling phenotypes.
This variant (p.Phe374Leu) is strongly associated with lighter skin, hair, and eye pigmentation, as well as an increased sensitivity to UV-induced skin damage.
The p.Phe374Leu variant in SLC45A2 is a major determinant of human pigmentation variation, influencing skin, hair, and eye color across global populations.
Promoter-associated regulatory variant implicated in hair and skin pigmentation variation across human populations.