USH2A rs104894343: Understanding This Genetic Variant
The rs104894343 variant is a specific genetic change located in the USH2A gene that alters the protein-building instructions for usherin. Research associates this variant with autosomal recessive retinitis pigmentosa and potential sensorineural hearing loss, though the clinical presentation can vary significantly between individuals.
What each genotype means
Typical USH2A genotype
This genotype represents the most common form of the USH2A gene in the general population. It is not associated with the specific pathogenic p.Cys759Phe variant linked to retinitis pigmentosa or Usher syndrome.
This is the most common genotype found in all global populations.
Carrier of USH2A variant
You carry one copy of the p.Cys759Phe variant. Because this condition is autosomal recessive, carrying a single copy typically does not cause symptoms, though it is important to be aware of this status for family planning.
Carried by roughly 0.3-0.5% of people of European ancestry, with lower frequencies in other global populations.
Increased risk for retinal disease
This genotype indicates you carry two copies of the p.Cys759Phe variant. While this variant is associated with autosomal recessive retinitis pigmentosa and Usher syndrome, its clinical impact can be variable, as some individuals with this genotype have been reported to be healthy. You should discuss these results with a genetic counselor or ophthalmologist to understand your specific clinical risk.
This genotype is rare, occurring at a very low frequency globally, though it is more frequently observed in certain European populations.
Understanding the rs104894343 Variant
The rs104894343 variant is a single nucleotide polymorphism (SNP) located within the USH2A gene. In genetic terms, this variant is a missense mutation, meaning it causes a change in the DNA sequence that results in a different amino acid being incorporated into the protein structure. Specifically, it involves the substitution of cysteine with phenylalanine at position 759 (p.Cys759Phe). This change can disrupt the structural integrity or function of the protein. The variant sits within a critical region of the gene, which is why researchers and clinicians pay close attention to its presence. While the location of a variant often dictates its functional impact, the biological consequences of rs104894343 are complex and depend on whether one or two copies of the variant are inherited. Understanding the precise location and nature of this change is the first step in contextualizing how it may influence human health.
The Role of the USH2A Gene
The USH2A gene provides instructions for making a protein called usherin. This protein is primarily found in the basement membranes of various tissues, including those in the inner ear and the retina of the eye. Usherin plays a crucial role in the development and maintenance of these specialized structures. In the inner ear, it is essential for the function of hair cells, which translate sound vibrations into electrical signals for the brain. In the retina, usherin is vital for the health and survival of photoreceptor cells, which are responsible for detecting light. When the USH2A gene is altered, the resulting usherin protein may be non-functional or unstable, potentially impairing the development or maintenance of these sensitive tissues. Consequently, pathogenic variants in this gene are frequently studied in the context of hereditary conditions that affect vision and hearing, such as Usher syndrome or non-syndromic retinitis pigmentosa.
Research and Clinical Evidence
The evidence linking rs104894343 to disease is primarily grounded in clinical genetics and observations of familial inheritance patterns. It is classified in databases such as ClinVar as a pathogenic variant, meaning it is widely recognized by the scientific community to contribute to specific clinical conditions when inherited in an autosomal recessive manner. This means that an individual generally needs to inherit two copies of the variant—one from each parent—to potentially manifest the associated conditions. However, the strength of the evidence is considered limited regarding the predictability of the phenotype; individuals with the same genotype can exhibit different levels of hearing or vision loss. Current research is focused on determining why these clinical variations occur and how other genetic or environmental factors might modulate the effect of this specific variant. It is important to note that this information is for educational purposes and should not be used to interpret personal health outcomes without professional guidance.
Population Frequency and Distribution
Data from the gnomAD database indicates that the rs104894343 variant is relatively rare on a global scale, with a minor allele frequency (MAF) of approximately 0.002. However, the frequency is not uniform across all human populations. It shows an elevated frequency in individuals of European descent, typically ranging between 0.3% and 0.5%. This distribution suggests that the variant may have originated or persisted in specific ancestral groups. Because it is rare in the general population, the likelihood of an individual inheriting two copies of this variant is low, unless they belong to a family or community with a higher prevalence of the variant. Genetic counseling services often use these frequency statistics to help families understand the probability of inheritance and the potential risk of passing the variant to offspring, especially when both biological parents are known carriers.
Interpreting Genetic Information
It is important to remember that genetic testing results are only one piece of a much larger health puzzle. If you have received information about your USH2A status, you cannot use this information alone to diagnose yourself or predict your future health. Many factors, including other genes, lifestyle, and environment, contribute to the development of vision and hearing conditions. You should never make medical decisions, such as starting or stopping treatments, based solely on a genetic report. If you are concerned about your results or family history, the most appropriate step is to discuss these findings with a certified genetic counselor or a medical specialist. These professionals can help you interpret your results in the context of your overall health and provide guidance on any potential follow-up steps.
How common is this variant?
The variant has a global minor allele frequency of approximately 0.002, with an elevated frequency in European populations ranging from 0.3% to 0.5%.
Frequently asked questions
What is Usher syndrome?
Usher syndrome is a genetic condition characterized by a combination of hearing loss and a progressive vision disorder called retinitis pigmentosa. It is inherited in an autosomal recessive pattern, meaning an affected individual must inherit two copies of a pathogenic gene variant.
Can a carrier of this variant develop symptoms?
Generally, individuals who carry only one copy of a recessive variant like rs104894343 do not manifest the associated clinical conditions. However, carriers should be aware of their status if they are planning to have children, as they have a chance of passing the variant to their offspring.
Does this variant guarantee vision or hearing loss?
No, the presence of the AA genotype indicates a higher genetic risk, but it does not guarantee that an individual will develop specific symptoms. Clinical presentation can vary widely due to other genetic and environmental factors.
Where can I find more information about my specific results?
If you have personal genetic data, you should consult with a healthcare provider or a genetic counselor. They can explain what your specific results mean in the context of your medical history and provide appropriate clinical context.
Sources & further reading
Educational information only, last refreshed 9/17/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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