ABCA4 rs61754395: Understanding the p.Leu541Pro Variant
The rs61754395 variant in the ABCA4 gene is a missense mutation that results in a leucine-to-proline substitution at position 541 of the protein. It is frequently identified in individuals with Stargardt disease, often acting as part of a complex allele that contributes to severe, childhood-onset retinal degeneration.
What each genotype means
Typical ABCA4 genotype
This genotype represents the common, non-variant sequence at this position in the ABCA4 gene. It is not associated with the specific pathogenic p.Leu541Pro change linked to Stargardt disease. Most individuals in the general population carry this genotype.
This is the most common genotype found in the general population across all ancestries.
Carrier of variant allele
You carry one copy of the p.Leu541Pro variant. Because ABCA4-related Stargardt disease is typically inherited in an autosomal recessive pattern, carrying a single copy is generally not sufficient to cause the condition on its own. However, this variant is often linked with other mutations in the same gene, and you should consult with a genetic counselor to understand your specific risk profile.
This genotype is rare, with the variant allele occurring at a global frequency of approximately 0.001, though it is more frequently observed in northern European populations.
Increased risk of Stargardt
You carry two copies of the p.Leu541Pro variant. This variant is recognized as a pathogenic change that, particularly when linked with other mutations like p.Ala1038Val, is associated with severe, childhood-onset Stargardt disease. Please discuss these results with a medical geneticist or ophthalmologist to determine if clinical evaluation is appropriate.
This genotype is extremely rare in the general population.
What is rs61754395?
The variant rs61754395, also known as c.1622T>C or p.Leu541Pro, is a specific change in the DNA sequence of the ABCA4 gene. In this variant, the nucleotide thymine is replaced by cytosine, which alters the resulting protein by substituting the amino acid leucine with proline at position 541. This change occurs within the coding region of the gene, which provides instructions for building the ABCA4 protein. Because this protein is essential for the normal function of photoreceptor cells in the eye, changes to its structure can have significant biological consequences. Researchers often study this variant because it is not just an isolated change; it is frequently found in combination with another variant, p.Ala1038Val, on the same chromosome. This pairing creates a 'complex allele' that is notably more impactful than either variant might be on its own, particularly in the context of inherited retinal diseases.
The Role of the ABCA4 Gene
The ABCA4 gene encodes a protein known as the ATP-binding cassette transporter, which is expressed exclusively in the photoreceptor cells of the retina. Its primary function is to transport a molecule called N-retinylidene-PE across the cell membrane, a critical step in the visual cycle that allows the eye to process light. Without a functional ABCA4 protein, toxic byproducts of the visual cycle can accumulate within the retina. This accumulation leads to the death of photoreceptor cells, which are the cells responsible for capturing light and sending signals to the brain. Because the retina is highly specialized, even minor disruptions in this transport process can lead to progressive vision loss. Mutations in ABCA4 are the most common cause of autosomal recessive Stargardt disease, a condition characterized by the degeneration of the macula, the part of the retina responsible for sharp, central vision.
Research and Clinical Associations
Scientific research has established a strong link between the p.Leu541Pro variant and various retinal dystrophies, most notably Stargardt disease. Evidence from clinical studies indicates that this variant is often found in a compound heterozygous state, meaning an individual carries one pathogenic variant on one chromosome and a different pathogenic variant on the other. The association is particularly strong when p.Leu541Pro is inherited alongside p.Ala1038Val. While the evidence for its pathogenicity is well-documented in the context of these complex alleles, the clinical presentation can vary significantly between individuals. Some patients may experience childhood-onset symptoms, while others might show a slower progression. It is important to note that while this variant is a known marker for disease risk, the presence of the variant alone does not guarantee a specific clinical outcome, as the overall genetic background and the specific combination of mutations play a major role in disease severity.
Population Frequency
The rs61754395 variant is relatively rare in the general population, with a global minor allele frequency (MAF) of approximately 0.001 according to gnomAD data. However, its distribution is not uniform across all groups. It is recognized as a founder variant in northern European populations, meaning it is more common in these groups due to historical population patterns. Because it is a rare variant, most individuals in the general population do not carry it. Its higher prevalence in specific ancestral groups highlights the importance of considering genetic ancestry when interpreting the significance of such variants in a clinical or research setting.
Navigating Genetic Information
Understanding your genetic profile regarding variants like rs61754395 can be complex. If you have received information about this variant, it is essential to understand that genetic testing results are not a medical diagnosis. The presence of a variant in the ABCA4 gene does not necessarily mean you will develop a retinal condition, as many factors, including the presence of a second mutation on the other chromosome, are required for the development of recessive conditions like Stargardt disease. You cannot 'fix' or 'change' this variant, and there are no lifestyle modifications that can alter your genetic sequence. If you are concerned about your eye health or the results of a genetic test, the most appropriate step is to consult with a genetic counselor or an ophthalmologist who specializes in inherited retinal diseases. They can provide context based on your personal and family medical history and help you understand what these findings mean for you.
How common is this variant?
The rs61754395 variant is rare, with a global minor allele frequency of approximately 0.001, though it is recognized as a founder variant in northern European populations.
Frequently asked questions
Is rs61754395 a diagnosis for Stargardt disease?
No, identifying this variant is not a diagnosis. Stargardt disease is a complex condition that typically requires the presence of two pathogenic mutations in the ABCA4 gene, and a clinical evaluation by an eye specialist is necessary for a formal diagnosis.
What should I do if I have the rs61754395 variant?
If you are concerned about your results, you should discuss them with a genetic counselor or an ophthalmologist. They can help you understand the implications of your specific genetic findings in the context of your family history and overall health.
Can I prevent vision loss if I carry this variant?
There is currently no way to prevent the genetic effects of this variant. However, regular check-ups with an eye care professional are recommended for anyone with a known genetic risk for retinal conditions to monitor eye health.
Why is this variant often linked to another mutation?
The p.Leu541Pro variant is frequently found in 'cis' with the p.Ala1038Val variant, meaning they are located on the same chromosome. This combination is known as a complex allele, which can have a more severe impact on the function of the ABCA4 protein.
Sources & further reading
Educational information only, last refreshed 9/17/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs61754395?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29Related variants in ABCA4
A variant in the ABCA4 gene associated with Stargardt disease.
Pathogenic missense variant in ABCA4 causing autosomal recessive Stargardt disease and cone-rod dystrophy.
Genomic variant within the ATP-binding cassette retinal transporter ABCA4 locus implicated in retinal degenerations and macular disease.
Known as the Gly1961Glu (G1961E) variant in ABCA4, a prevalent hypomorphic mutation contributing to late-onset Stargardt disease and cone-rod dystrophy.
A well-documented pathogenic missense change in ABCA4 causing autosomal recessive Stargardt disease and cone-rod dystrophy.
Pathogenic missense variant in ABCA4 (p.Leu541Pro) causing Stargardt disease and juvenile macular dystrophy.