ABCA4 rs61754401: Understanding the p.Gly1961Glu Variant
The rs61754401 variant in the ABCA4 gene is a well-characterized genetic change known as p.Gly1961Glu. It is primarily associated with a milder, late-onset form of Stargardt disease, a condition that affects the macula of the eye.
What each genotype means
Typical ABCA4 function
This genotype represents the common, non-variant form of the ABCA4 gene at this position. Individuals with this profile do not carry the p.Gly1961Glu mutation associated with late-onset Stargardt disease.
This is the most common genotype globally, found in the vast majority of the human population.
Carrier of hypomorphic variant
This genotype indicates you carry one copy of the p.Gly1961Glu variant. Research suggests this is a hypomorphic allele, which may be associated with late-onset Stargardt disease, particularly if inherited alongside a second, more severe ABCA4 mutation.
Carried by roughly 0.5% to 1% of individuals in European and African populations, and is less common in other global populations.
Increased risk of macular dystrophy
This genotype means you carry two copies of the p.Gly1961Glu variant. This is associated with late-onset Stargardt disease, often characterized by milder, localized macular changes and foveal-sparing atrophy compared to more severe ABCA4 mutations.
This homozygous genotype is rare, occurring at a very low frequency in the general population.
What is the rs61754401 Variant?
The rs61754401 variant is a specific change in the DNA sequence of the ABCA4 gene, located on chromosome 1. In scientific literature, this variant is frequently referred to by its protein-level change, p.Gly1961Glu, which indicates that the amino acid glycine at position 1961 has been replaced by glutamic acid. This type of change is known as a missense mutation. Because the ABCA4 gene provides instructions for making a protein that is essential for the health of photoreceptor cells in the retina, changes in this gene can disrupt normal visual function. The rs61754401 variant is considered a hypomorphic allele, meaning it results in a protein that retains some, but not all, of its original function. This partial loss of function is a key reason why this specific variant is often associated with a more gradual or later-onset progression of retinal symptoms compared to other, more severe mutations in the same gene.
The Role of the ABCA4 Gene
The ABCA4 gene encodes a protein called the ATP-binding cassette transporter, subfamily A, member 4. This protein acts as a molecular pump within the light-sensitive cells of the retina, known as rods and cones. Its primary job is to transport a byproduct of the visual cycle, N-retinylidene-phosphatidylethanolamine, out of the photoreceptor discs. If this process is impaired, toxic byproducts can accumulate, leading to the formation of lipofuscin, a yellow-brown pigment that builds up in the retinal pigment epithelium. Over time, the accumulation of these toxic substances can damage the cells of the macula, the central part of the retina responsible for sharp, detailed vision. Because the ABCA4 protein is so critical for maintaining the chemical balance required for sight, variants that significantly reduce its activity are the most common genetic cause of inherited macular degeneration, including Stargardt disease.
Research and Clinical Associations
Research has established a strong link between the p.Gly1961Glu variant and a specific clinical presentation of Stargardt disease. Unlike early-onset forms of the disease that can cause rapid vision loss in childhood, individuals carrying this variant often experience a later onset of symptoms. A hallmark of this specific variant is 'foveal-sparing' macular atrophy, meaning that the very center of the macula, which is responsible for the sharpest vision, may remain relatively preserved for a longer period. While the evidence for this association is well-documented in clinical genetics, it is important to note that the severity of the condition can be influenced by other genetic factors, including the presence of a second variant on the other copy of the ABCA4 gene. Because Stargardt disease is inherited in an autosomal recessive pattern, the clinical outcome often depends on the combination of variants an individual inherits from both parents.
Understanding Your Genetic Information
Genetic information regarding variants like rs61754401 is intended for educational and research purposes. It is important to understand that having a specific genotype does not provide a medical diagnosis. If you have concerns about your vision or a family history of retinal conditions, the most appropriate step is to consult with an ophthalmologist or a certified genetic counselor. These professionals can provide context based on your personal health history and clinical eye examinations. You cannot 'fix' or 'change' a genetic variant, but understanding your genetic profile can help you and your healthcare provider make informed decisions about monitoring your eye health. Always discuss any findings from genetic testing with a qualified clinician who can interpret the results within the context of your overall health and provide guidance on appropriate screening or management strategies.
How common is this variant?
The rs61754401 variant has a global minor allele frequency of approximately 0.005, though it is more common in African and European populations, where frequencies reach 0.5% to 1%.
Frequently asked questions
What is Stargardt disease?
Stargardt disease is an inherited condition that causes progressive vision loss due to the degeneration of the macula. It is most commonly caused by variants in the ABCA4 gene.
Is rs61754401 the same as p.Gly1961Glu?
Yes, rs61754401 is the identifier for the specific DNA change, while p.Gly1961Glu describes the resulting change in the protein's amino acid sequence.
Does having this variant mean I will go blind?
Not necessarily. This variant is associated with a milder, late-onset form of the disease that often spares the central vision for a long time. Clinical outcomes vary significantly between individuals.
How is this variant inherited?
This variant is inherited in an autosomal recessive manner. This means that an individual typically needs to inherit two copies of a pathogenic variant to be at risk for the associated condition.
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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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.