BEST1 rs28936682: Understanding This Rare Genetic Variant
The rs28936682 variant is a rare genetic change located in the BEST1 gene. It is associated with Best vitelliform macular dystrophy, an inherited condition that affects the retina.
What each genotype means
Typical risk profile
You carry two copies of the common reference allele for the BEST1 gene. This genotype is not associated with Best vitelliform macular dystrophy or related bestrophinopathies. It reflects the standard baseline profile observed in the general population.
Carried by more than 99.9% of individuals across all major continental populations.
Increased macular dystrophy risk
You carry one copy of the pathogenic missense variant p.Thr6Arg in the BEST1 gene. Because Best vitelliform macular dystrophy is inherited in an autosomal dominant manner, carrying a single copy is associated with a significantly elevated risk of developing macular lesions and central vision changes, though age of onset and severity can vary. These findings are statistical associations from medical literature and do not represent a clinical diagnosis.
Extremely rare; observed in fewer than 1 in 10,000 individuals worldwide (gnomAD MAF < 0.0001).
Elevated bestrophinopathy risk
You carry two copies of the pathogenic BEST1 missense variant. Homozygous inheritance for dominant BEST1 pathogenic variants is extraordinarily rare in published clinical studies and is expected to confer a very high risk for severe retinal pathology, including autosomal recessive bestrophinopathy-like presentations. A clinical evaluation with an ophthalmologist or eye specialist is typically recommended for individuals with pathogenic BEST1 variants.
Exceedingly rare, with essentially zero homozygotes identified in standard general reference population databases.
What is the rs28936682 Variant?
The rs28936682 variant is a specific change in the DNA sequence of the BEST1 gene. In genetic terms, this is a missense variant, meaning it results in a single amino acid substitution—specifically, the replacement of threonine with arginine at position 6 (p.Thr6Arg) in the bestrophin-1 protein. This variant is cataloged in scientific databases as a pathogenic change, meaning it is known to disrupt the normal function of the protein it encodes. Because the BEST1 gene is critical for the health of the retinal pigment epithelium, changes in its sequence can have significant impacts on vision. This variant is primarily studied in the context of inherited retinal dystrophies, where it acts as a genetic marker for specific clinical presentations.
The Role of the BEST1 Gene
The BEST1 gene provides the instructions for creating a protein called bestrophin-1. This protein functions as an ion channel, specifically a chloride channel, located in the basolateral plasma membrane of the retinal pigment epithelium (RPE). The RPE is a layer of cells that supports the light-sensing photoreceptors in the eye. By regulating the flow of chloride ions, bestrophin-1 helps maintain the proper environment for these photoreceptors to function. When the BEST1 gene contains a pathogenic variant, the resulting bestrophin-1 protein may be misfolded, unstable, or unable to transport ions correctly. This dysfunction can lead to the accumulation of fluid or deposits under the retina, which is a hallmark of the group of conditions known as bestrophinopathies.
Clinical Associations and Evidence
Research associates the rs28936682 variant with Best vitelliform macular dystrophy (BVMD), also known as Best disease. This is an autosomal dominant condition, meaning that inheriting a single copy of the variant from one parent is typically sufficient to manifest the associated phenotype. The evidence for this association is grounded in clinical observations of individuals who present with characteristic macular lesions and abnormal electro-oculogram (EOG) results. While over 250 pathogenic variants have been identified in the BEST1 gene, rs28936682 is specifically recognized for its role in altering the channel's function. It is important to note that the clinical expression of BEST1 variants can be highly variable, even among family members carrying the same genetic change, which is a common feature of bestrophinopathies.
Population Frequency
The rs28936682 variant is classified as extremely rare in the general population. According to data from the Genome Aggregation Database (gnomAD), the minor allele frequency (MAF) is less than 0.0001. Because it is so uncommon, it is not typically found in the general population and is usually identified only in clinical settings where individuals are being tested for specific retinal symptoms. Its rarity means that large-scale population studies have limited data on its distribution across different ancestral groups. Most of the information regarding this variant comes from case studies and clinical cohorts of patients already diagnosed with or suspected of having a retinal dystrophy.
What This Information Means for You
If you or a family member have been identified as a carrier of the rs28936682 variant, it is essential to understand that this is a clinical finding that requires professional interpretation. Genetic testing results should always be discussed with a medical geneticist or an ophthalmologist who specializes in inherited retinal diseases. These professionals can provide context based on your specific clinical history and family background. This information is for educational purposes and does not constitute a medical diagnosis or a treatment plan. If you are concerned about your vision or the risk of passing this variant to future generations, consult with a healthcare provider to discuss genetic counseling and appropriate monitoring strategies. Never make changes to your health management based solely on genetic data without clinical guidance.
How common is this variant?
The rs28936682 variant is extremely rare, with a minor allele frequency (MAF) of less than 0.0001 in the gnomAD database.
Frequently asked questions
What is Best vitelliform macular dystrophy?
Best vitelliform macular dystrophy is an inherited eye condition that causes the buildup of yellowish, egg-yolk-like deposits under the retina. It can lead to vision loss over time, though the severity varies significantly between individuals.
Is rs28936682 the only cause of Best disease?
No, Best disease is associated with over 250 different pathogenic variants in the BEST1 gene. The rs28936682 variant is just one of many possible genetic changes that can lead to this condition.
Can I be tested for this variant?
Yes, genetic testing for BEST1 variants is available through clinical laboratories, often ordered by ophthalmologists or genetic counselors. You should discuss the necessity and implications of such testing with your doctor.
Does having this variant guarantee vision loss?
While this variant is associated with retinal dystrophy, the clinical expression is highly variable. Not everyone with the variant will experience the same degree of vision loss, and some may have very mild symptoms.
Sources & further reading
Educational information only, last refreshed 10/20/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Encodes the Thr6Arg (T6R) missense change in Bestrophin 1 associated with autosomal dominant Best vitelliform macular dystrophy.
A missense alteration in bestrophin-1 linked to Best vitelliform macular dystrophy and central visual impairment.
Pathogenic missense variant in BEST1 (p.Ala146Thr) linked to autosomal dominant Best vitelliform macular dystrophy causing progressive loss of central vision.
Missense mutation in BEST1 causing classical Best vitelliform macular dystrophy type 2.
A pathogenic missense variant (p.Tyr227Asn) in BEST1 associated with Best vitelliform macular dystrophy.
Pathogenic missense mutation (p.Arg218Cys) in bestrophin-1 causing Best vitelliform macular dystrophy with subretinal egg-yolk-like lesions.