CFH rs35292876: Understanding This Low-Frequency Genetic Variant
The rs35292876 variant is a low-frequency genetic marker located within the CFH gene, which encodes a critical regulator of the human complement system. Researchers study this variant as part of polygenic risk models to better understand the complex genetic architecture of age-related macular degeneration (AMD).
What each genotype means
Typical risk profile
You carry two copies of the common reference allele for this complement factor H variant. Published research indicates that this baseline genotype is not associated with the increased risk of age-related macular degeneration observed with the rare alternate allele. Because evidence for this specific variant is limited and multifaceted, overall vision health depends on broader lifestyle and multigenic risk factors.
Found in more than 98% of individuals across global populations.
Modestly increased susceptibility
You carry one copy of the uncommon T allele evaluated in studies of complement-mediated eye conditions. Genome-wide analyses have statistically associated this rare variant with an increased risk of age-related macular degeneration, often as part of specific risk haplotypes in European cohorts. Because current scientific evidence remains limited and penetrance varies across ancestries, carrying this allele does not diagnose any condition or ensure vision loss.
Carried by approximately 1% to 2% of people in European and American cohorts, and is extremely rare or absent in other ancestries.
Elevated susceptibility profile
You carry two copies of the rare alternative allele evaluated in complement factor H association studies. While statistical association studies link this allele to increased susceptibility to age-related macular degeneration, homozygous individuals are exceptionally rare in published research cohorts. The full clinical impact of carrying two copies remains under active investigation with limited empirical data, and it is not a direct medical diagnosis.
Extremely rare globally, occurring in fewer than 1 in 10,000 individuals across most reference populations.
What is rs35292876?
The rs35292876 variant is a single-nucleotide polymorphism (SNP) situated within the CFH gene on chromosome 1. In genetic databases, it is classified as a synonymous variant, meaning that while it represents a change in the DNA sequence, it does not alter the amino acid sequence of the resulting protein. Because it is a low-frequency variant, it is not as widely studied as common markers like the well-known Y402H polymorphism. Scientists often include this SNP in large-scale genomic studies to determine if it contributes to the overall genetic liability for complex eye conditions. It is important to note that being a synonymous change, its functional impact on the CFH protein remains a subject of ongoing investigation rather than established fact.
The Role of the CFH Gene
The CFH gene provides instructions for making complement factor H, a protein that plays a vital role in the innate immune system. Specifically, it acts as a primary regulator of the alternative complement pathway, preventing the immune system from accidentally attacking the body's own healthy tissues. When the complement system is overactive or dysregulated, it can lead to chronic inflammation. In the context of the eye, this inflammation is thought to contribute to the development of age-related macular degeneration (AMD), a condition that affects the macula and can lead to central vision loss. Because CFH is so central to controlling this inflammatory response, variations within this gene are frequently scrutinized for their potential to influence how the body manages complement activity over a lifetime.
Research and Evidence Strength
Current research into rs35292876 is characterized by limited evidence regarding its direct clinical impact. While it has been identified as a lead variant in some genetic association studies concerning AMD, it is often analyzed alongside other markers in the CFH and CFHR gene cluster. Some studies have noted that this variant is part of specific risk haplotypes, yet it has not been consistently associated with changes in systemic factor H concentrations. Because the evidence is currently limited, it is not used as a standalone diagnostic tool. Instead, it serves as a data point in complex polygenic risk scores, which attempt to aggregate the effects of many different genetic variants to estimate a person's relative susceptibility to eye disease. Further research is required to clarify its specific biological contribution.
Population Frequency
The rs35292876 variant is considered a low-frequency variant, with a minor allele frequency (MAF) typically reported at less than 2% across most worldwide reference populations. Because it is relatively rare, it is not found in the majority of the population. Its distribution can vary between different ancestral groups, which is a common feature of low-frequency genetic markers. Researchers use large-scale databases like gnomAD to track these frequencies, which helps in determining whether a variant is common enough to be studied in general population cohorts or if it is restricted to specific subpopulations. The low frequency of this variant means that most individuals will carry the common, non-variant allele at this position.
What This Information Means for You
Genetic information regarding variants like rs35292876 is intended for educational and research purposes. It is not a medical diagnosis and cannot predict with certainty whether an individual will develop a specific condition. AMD is a multifactorial disease influenced by a combination of genetics, environmental factors, and lifestyle choices, such as smoking and diet. If you are concerned about your eye health or have a family history of macular degeneration, the most effective step is to consult with an eye care professional, such as an ophthalmologist or optometrist. They can provide comprehensive screenings and personalized advice based on your clinical history. Never make changes to your health management or medical decisions based solely on genetic data without first discussing them with a qualified healthcare provider.
How common is this variant?
The rs35292876 variant is a low-frequency marker with a minor allele frequency of less than 2% across worldwide populations.
Frequently asked questions
Is rs35292876 a cause of macular degeneration?
No, this variant is not considered a direct cause of macular degeneration. It is a genetic marker that has been statistically associated with the condition in some research studies, but it does not guarantee the development of the disease.
Should I get tested for this CFH variant?
Routine genetic testing for this specific variant is not currently recommended for the general public. If you have concerns about your risk for eye disease, you should speak with an eye care professional about clinical risk factors and appropriate screening.
Can I change my risk if I have this variant?
While you cannot change your genetics, you can manage modifiable risk factors for eye health. Maintaining a healthy diet, avoiding smoking, and getting regular eye exams are standard recommendations for supporting long-term vision health.
Where can I find more information on CFH variants?
You can find reliable information on genetic variants through resources like MedlinePlus Genetics or the NCBI's ClinVar database. These platforms provide curated, evidence-based summaries of genetic research.
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 in the complement factor H gene is associated with altered regulation of the alternative complement pathway and increased susceptibility to age-related macular degeneration.
This regulatory variant in the CFH locus is linked to complement system dysregulation and is a recognized genetic risk factor for age-related macular degeneration.
Intronic single nucleotide variant in the CFH region associated with susceptibility to age-related macular degeneration (AMD).
Common variant in the CFH locus strongly associated with risk of age-related macular degeneration (AMD).
Genomic marker in CFH frequently co-inherited in haplotypes modulating risk of late-stage visual loss from macular degeneration.
Intronic marker in CFH forming critical susceptibility haplotypes for choroidal neovascularization and macular atrophy.