HERC2 rs1667397: Understanding Your Eye Color Genetics
The rs1667397 variant is a single nucleotide polymorphism located within the HERC2 gene. It serves as a significant regulatory marker that influences the expression of the nearby OCA2 gene, which plays a central role in determining human eye color.
What each genotype means
Typical darker pigmentation tendency
You carry two copies of the ancestral A allele at rs1667397. This genotype is statistically associated with a baseline likelihood of darker eye, hair, and skin pigmentation, reflecting typical OCA2 gene regulatory activity. Your actual eye color and appearance are influenced by multiple interacting genes across the OCA2-HERC2 locus and the broader genome.
Carried by approximately 55% to 70% of people of European ancestry and the vast majority of individuals of African and East Asian descent.
Intermediate pigmentation tendency
You carry one copy of the derived G allele and one copy of the ancestral A allele. Having a single G allele at this position is correlated with lighter eye and skin pigmentation haplotypes, often found in individuals with intermediate, green, or hazel eyes. Because pigmentation traits are polygenic, the final phenotypic presentation depends heavily on surrounding variants such as HERC2 rs12913832.
Carried by roughly 30% to 35% of individuals of European ancestry; it is rare in East Asian and African populations.
Lighter eye and skin tendency
You carry two copies of the derived G allele at rs1667397. In population studies, this homozygous genotype tracks with haplotypes that decrease melanocyte pigment production, conferring a significantly increased statistical probability of blue, light hazel, or green eyes as well as fairer skin. However, eye color expression is determined collectively with other key regulatory loci, particularly in the adjacent HERC2 gene.
Found in approximately 2% to 6% of European populations and is extremely uncommon in non-European ancestries.
What is rs1667397 and Where is it Located?
The variant rs1667397 is a specific genetic change, or single nucleotide polymorphism (SNP), situated within the HERC2 gene. Specifically, it is located in an intronic region, which means it resides in a non-coding part of the gene that does not provide instructions for building proteins directly. Instead, this region acts as a regulatory element. Research has identified this area of the HERC2 gene as a critical hub for controlling the activity of the neighboring OCA2 gene. By sitting in this conserved regulatory sequence, rs1667397 helps determine how much of the OCA2 protein is produced, which in turn dictates the amount of melanin pigment deposited in the iris of the eye.
The Role of the HERC2 and OCA2 Genes
The HERC2 gene is physically located adjacent to the OCA2 gene on chromosome 15. While HERC2 has its own cellular functions, its intronic regions are famous in genetics for their role in pigmentation. The OCA2 gene provides instructions for making the P protein, which is essential for the maturation of melanosomes—the structures in cells that produce and store melanin. When the regulatory elements within HERC2 are active, they promote the expression of OCA2. If these regulatory signals are altered, OCA2 expression may decrease, leading to lower melanin production in the iris. This reduction in pigment is the primary biological mechanism that results in lighter eye colors, such as blue, rather than brown.
Research Associations and Evidence Strength
The association between the HERC2-OCA2 locus and eye color is one of the most well-documented findings in human genetics. Multiple genome-wide association studies (GWAS) have consistently identified variants in this region as the primary drivers of eye color variation in populations of European ancestry. The evidence strength for the role of this locus is considered moderate to high, as it explains a large proportion of the phenotypic variance observed in human eye color. While rs1667397 is a key marker, it is often studied alongside other nearby SNPs, such as rs12913832, to form haplotypes that predict eye color with high accuracy. It is important to note that eye color is a polygenic trait, meaning other genes and environmental factors also contribute to the final appearance.
Population Frequency and Distribution
The rs1667397 variant is most commonly observed in populations of European ancestry. Research indicates that the specific haplotypes associated with this region have been subject to evolutionary selection in these groups. In contrast, the variant is significantly less common or absent in many other global population groups. Because eye color variation is highly diverse, the frequency of this SNP can vary even within European sub-populations. It is a classic example of how specific genetic markers can become concentrated in certain geographic regions due to historical migration and selective pressures, making it a valuable tool for researchers studying human population genetics and the evolution of physical traits.
What This Information Means for You
Understanding your genotype at rs1667397 provides insight into the genetic factors that contribute to your eye color. However, it is important to remember that genetics is complex and rarely deterministic. While this variant is a strong predictor, it does not account for every nuance of eye color, which can be influenced by a combination of multiple genes and their interactions. This information is for educational purposes only and should not be used for medical diagnosis or to make health-related decisions. If you have questions about your genetic results or how they relate to your physical traits, you may find it helpful to consult with a genetic counselor or a qualified healthcare professional who can provide context based on your full genetic profile.
How common is this variant?
The rs1667397 variant is common in European populations, where it has been subject to evolutionary selection, but it is largely absent or rare in other global populations.
Frequently asked questions
Does this SNP determine my eye color?
While rs1667397 is a major factor in eye color, it is not the only one. Eye color is a polygenic trait, meaning it is influenced by several different genes and their interactions.
Can I use this to predict my child's eye color?
Genetic testing can show the presence of certain variants, but predicting a child's eye color is complex. Because multiple genes are involved, it is not possible to guarantee an outcome based on a single SNP.
Is this variant linked to any health conditions?
The HERC2-OCA2 locus is primarily associated with pigmentation. While it is a major factor in eye color, it is not typically used as a diagnostic tool for medical conditions.
Why is this variant common in Europeans?
Research suggests that specific variants in the HERC2-OCA2 region underwent positive selection in European populations. This led to an increase in the frequency of alleles associated with lighter eye and hair pigmentation.
Sources & further reading
Educational information only, last refreshed 10/27/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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A well-documented marker in the HERC2/OCA2 region strongly associated with blue vs. brown eye color variation.
Intronic regulatory modifier in HERC2 acting as an enhancer upstream of OCA2 to fine-tune human iris pigmentation and hair shade traits.
A non-coding variant in the HERC2 regulatory region that modulates OCA2 expression and eye color.
Variant in the HERC2-OCA2 regulatory locus significantly associated with iris pigmentation and blue versus non-blue eye color variation.
Strongly determines human eye color; the C allele is associated with blue eye color and the T allele with brown eye color via long-range regulation of the OCA2 promoter.
Regulatory SNP in HERC2 that modulates OCA2 expression, serving as a primary determinant of human eye color.