HERC2 rs1667393: Understanding Eye Color Genetics
The rs1667393 variant is a genetic marker located within the HERC2 gene on chromosome 15. It is part of a regulatory region strongly associated with human iris pigmentation and the variation of eye color in populations of European ancestry.
What each genotype means
Likely brown eye pigmentation
Carrying two copies of the C allele at rs1667393 is statistically associated with darker iris pigmentation, such as brown eyes, particularly when co-inherited with standard OCA2-HERC2 regulatory haplotypes. However, because human eye color is a polygenic trait modulated by multiple interacting variants across several genes, having this genotype alone does not guarantee a specific eye color. Evidence for rs1667393 as an independent causal driver remains limited compared to the primary regulatory variant rs12913832.
Found in approximately 4% to 7% of individuals of non-Finnish European ancestry, but represents the predominant genotype in most African and East Asian populations.
Intermediate iris pigmentation likelihood
Carrying one C allele and one T allele is associated with an intermediate probability between lighter and darker iris shades, such as green, hazel, or brown. Because eye color is polygenic and depends heavily on adjacent regulatory variants like rs12913832, this variant's standalone predictive utility is limited. The actual color of your eyes depends on a broader combination of pigment-related genes across your genome.
Carried by approximately 30% to 35% of individuals of European descent, while being considerably less common in African and East Asian ancestries.
Likely lighter eye pigmentation
Having two copies of the T allele is correlated with lighter eye color, such as blue or green, largely due to linkage disequilibrium with regulatory variants in the HERC2-OCA2 locus. Research indicates that while rs1667393 is tightly linked to European light-pigmentation haplotypes, its direct functional impact is considered secondary or limited compared to the primary causal variant rs12913832. Eye color expression remains complex and is influenced by multiple additional genomic loci.
Carried by roughly 60% of people of non-Finnish European ancestry, but rare to absent in most non-European populations.
What is rs1667393?
The rs1667393 variant is a single nucleotide polymorphism (SNP) situated within the HERC2 gene on chromosome 15q13.1. This specific region of the human genome is highly significant for its role in pigmentation. While rs1667393 is a recognized marker in this area, it is often studied alongside other nearby variants, such as the well-characterized rs12913832, which is widely considered a primary regulatory element for the neighboring OCA2 gene. Because these variants are located in a region with complex linkage disequilibrium—where multiple genetic markers are inherited together—rs1667393 serves as a useful tool for researchers investigating the genetic architecture of human appearance. It sits within an intronic region, meaning it does not code for a protein itself but is instead involved in the complex regulatory machinery that dictates how other genes are expressed in the body.
The Role of HERC2 and OCA2
The HERC2 gene is located immediately adjacent to the OCA2 gene, and the two function in a coordinated manner to influence pigmentation. The OCA2 gene provides instructions for making the P protein, which is essential for the normal development and function of melanosomes—the structures in cells that produce and store melanin. Melanin is the pigment that determines the color of our skin, hair, and eyes. Research indicates that the HERC2 gene contains regulatory elements that act as 'switches' for the OCA2 gene. When these regulatory regions are altered, they can inhibit or reduce the expression of OCA2, leading to lower levels of melanin production in the iris. This reduction in melanin is a primary driver of lighter eye colors, such as blue, in human populations. Consequently, variations in the HERC2-OCA2 region are considered the most significant genetic determinants of eye color variation.
Research and Evidence Strength
The association between the HERC2-OCA2 region and eye color is supported by extensive genome-wide association studies (GWAS). While the evidence linking this genomic region to iris pigmentation is robust, the specific contribution of individual SNPs like rs1667393 is often categorized as having limited or moderate evidence when viewed in isolation, compared to the primary causal signals identified in the region. Researchers use these markers to build predictive models for eye color, which have applications in fields like forensic genetics. However, it is important to note that eye color is a polygenic trait, meaning it is influenced by many different genes and environmental factors. While the HERC2-OCA2 locus explains a large proportion of the variation, it does not account for every nuance of eye color, and other loci also play supporting roles in determining the final phenotype.
Population Frequency
The frequency of variants in the HERC2-OCA2 region varies significantly across different global populations. The alleles associated with lighter eye pigmentation are most common in European populations, where they have been subject to specific evolutionary pressures. In contrast, these derived alleles are often absent or found at very low frequencies in African and East Asian populations. According to data from the gnomAD database, the minor allele frequency (MAF) for rs1667393 is approximately 0.21 globally, but this number rises significantly to around 0.78 in non-Finnish European (NFE) populations. This stark difference in frequency highlights the unique genetic history of pigmentation traits in different parts of the world and underscores why findings from one ancestral group cannot always be generalized to others.
Interpreting Your Genetic Information
Understanding your genotype for a variant like rs1667393 provides insight into the genetic factors that contribute to your physical traits, specifically eye color. However, it is important to recognize the limitations of this information. Genetic testing for pigmentation markers is primarily for educational or ancestral interest and cannot provide a perfect prediction of physical appearance due to the complex, polygenic nature of these traits. This information is not diagnostic and does not indicate any health risks or medical conditions. 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. Always remember that your genetic makeup is only one part of the story, and environmental factors also play a role in how your traits are expressed.
How common is this variant?
The rs1667393 variant is common in European populations, with a minor allele frequency of approximately 0.78 in non-Finnish Europeans, compared to a global frequency of about 0.21.
Frequently asked questions
Can a DNA test accurately predict my exact eye color?
While genetic tests can identify markers like those in the HERC2-OCA2 region that influence eye color, they cannot predict your exact eye color with 100% accuracy. Eye color is a complex, polygenic trait influenced by multiple genes and environmental factors that are not fully captured by a single SNP.
Is the HERC2 gene associated with any health conditions?
The HERC2 gene is primarily studied for its role in pigmentation. While mutations in the nearby OCA2 gene can cause oculocutaneous albinism, the common variants in the HERC2 regulatory region discussed here are generally associated with normal variation in eye color rather than disease.
Why do my eye color results differ from my actual eye color?
Genetic markers provide a probability based on population-wide associations. Because eye color is influenced by many genes, your specific combination of variants may result in a phenotype that differs from the most common outcome associated with a single SNP.
Are these eye color variants found in all populations?
No, the specific variants in the HERC2-OCA2 region that are strongly associated with light eye color are most common in European populations. They are often absent or very rare in African and East Asian populations.
Sources & further reading
Educational information only, last refreshed 10/18/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This variant is located in an intron of HERC2 and acts as a major regulatory marker for OCA2 expression, strongly influencing human eye color variation.
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.