CYP1B1 rs61752480: Glaucoma Risk and Evidence Explained
The genetic variant rs61752480 is a missense single-nucleotide polymorphism located in the CYP1B1 gene that results in the amino acid substitution p.Ala119Ser. Scientific literature has explored its association with early-onset ocular conditions, notably primary congenital glaucoma and juvenile open-angle glaucoma. However, clinical databases categorize the available evidence for this specific variant as limited or inconclusive, often regarding it as a mild modifier or benign population polymorphism rather than an independent causative mutation.
What each genotype means
Typical risk profile
You carry two copies of the standard G allele encoding alanine at position 119 of the CYP1B1 enzyme. This genotype is associated with normal baseline enzyme function and does not confer elevated genetic susceptibility to CYP1B1-related forms of glaucoma. Research indicates typical ocular development without the risk modifications observed with alternative missense alleles.
Found in approximately 90% to 96% of individuals across global populations in gnomAD.
Modestly altered glaucoma risk
You carry one copy of the T allele encoding the p.Ala119Ser missense change in CYP1B1 alongside one typical allele. Biallelic loss-of-function variants in CYP1B1 are well known to cause autosomal recessive primary congenital glaucoma, but the clinical significance of carrying a single p.Ala119Ser allele remains limited and controversial in published literature. Studies suggest heterozygous carriers generally have normal ocular health, though some investigations explore whether it slightly modifies open-angle glaucoma susceptibility.
Carried by approximately 4% to 9% of individuals globally, with varying frequencies across diverse ancestries.
Altered CYP1B1 function
You carry two copies of the T allele encoding the p.Ala119Ser substitution in the CYP1B1 gene. Homozygous or compound heterozygous alterations in CYP1B1 have been evaluated in the context of primary congenital and juvenile open-angle glaucoma, although evidence specifically linking p.Ala119Ser alone to disease penetrance is limited and classified with variable pathogenicity in databases like ClinVar. Because evidence is limited, this finding alone does not establish a diagnosis; individuals with a family history of ocular pressure disorders should discuss routine eye examinations with an eye care specialist.
Rare globally, occurring in fewer than 1 in 400 individuals (under 0.3%) in most population groups.
Variant Details and Genomic Context
The single-nucleotide polymorphism rs61752480 corresponds to a base substitution on chromosome 2 within the CYP1B1 gene. In coding coordinates, this nucleotide transition alters the protein sequence at residue 119, substituting the standard amino acid alanine with a serine (designated p.Ala119Ser or A119S). Because this change alters the underlying amino acid sequence, it is classified as a missense variant. In genetic databases like dbSNP and ClinVar, this locus is cataloged alongside hundreds of other coding variants that have been sequenced across healthy cohorts and individuals with ocular phenotypes.
Biological Role of the CYP1B1 Gene
The CYP1B1 gene encodes cytochrome P450 family 1 subfamily B member 1, a membrane-bound monooxygenase enzyme localized to the endoplasmic reticulum. CYP1B1 participates in the oxidative metabolism of various endogenous compounds, such as steroid hormones and polyunsaturated fatty acids, as well as exogenous xenobiotics. Crucially, research indicates that CYP1B1 plays an essential structural and developmental role during embryonic ocular morphogenesis. Deficiencies or disruptions in functional CYP1B1 activity can impair the proper development of the trabecular meshwork and Schlemm's canal, which are structures essential for aqueous humor drainage in the anterior segment of the eye.
Scientific Evidence and Glaucoma Associations
Disruptive mutations in CYP1B1 are well-established causes of primary congenital glaucoma (PCG) and contribute to juvenile open-angle glaucoma (JOAG). However, the specific evidence tying rs61752480 directly to disease causation is graded as limited. While some early candidate-gene studies identified p.Ala119Ser in cohorts with early-onset glaucoma, modern population databases have revealed that the minor allele is reasonably common in healthy individuals. ClinVar classifications for rs61752480 reflect this nuance, generally interpreting it as benign, likely benign, or a variant of uncertain significance. Rather than acting as a fully penetrant disease-causing mutation on its own, it may represent a common polymorphic variant or a low-effect modifier.
Population Frequency and Allele Distribution
Data from large-scale reference cohorts like the Genome Aggregation Database (gnomAD) show that rs61752480 is present at non-negligible levels across several global populations. The overall minor allele frequency typically falls between 0.02 and 0.05 (2% to 5%). Because severe Mendelian congenital glaucoma typically has an incidence of roughly 1 in 10,000 to 18,000 births, an allele present in up to 5% of healthy individuals cannot act as a classical high-penetrance Mendelian driver by itself. Its distribution illustrates the importance of modern population databases in distinguishing harmless background variation from rare pathogenic defects.
What to Do With Genetic Information
Discovering an altered genotype at rs61752480 on a consumer or research panel does not mean you have or will develop glaucoma. The scientific evidence connecting this specific change directly to disease pathogenesis is limited, and it does not serve as a diagnostic marker. Genetic data should never replace regular ophthalmic care or clinical exams. If you have concerns about your ocular health, elevated intraocular pressure, or a family history of congenital or juvenile glaucoma, schedule a comprehensive eye examination with an optometrist or ophthalmologist and consult a certified genetic counselor to interpret your family history.
How common is this variant?
The minor allele frequency for rs61752480 ranges approximately between 0.02 and 0.05 across global populations in gnomAD, with the heterozygous genotype occurring in a modest percentage of healthy individuals worldwide.
Frequently asked questions
Does carrying the rs61752480 variant mean I will get glaucoma?
No. The presence of this variant does not mean you will develop glaucoma. Current scientific evidence regarding rs61752480 is classified as limited, and the variant is frequently identified in healthy individuals without ocular disease.
What is the difference between primary congenital glaucoma and open-angle glaucoma?
Primary congenital glaucoma (PCG) is a rare, severe condition present at birth or early infancy caused by structural malformations in the eye drainage system. Juvenile and adult open-angle glaucoma usually develop later in life and involve progressive damage to the optic nerve often related to increased intraocular pressure.
Why is the evidence for rs61752480 described as limited?
Early studies found this variant in individuals with early-onset glaucoma, but subsequent large-scale population studies revealed that it is relatively common in healthy individuals. Because its frequency is much higher than the prevalence of congenital glaucoma, it is generally considered a benign polymorphism or low-penetrance factor.
Should I see an eye doctor if my genetic test shows this variant?
Routine comprehensive eye exams are recommended for everyone regardless of genetics, particularly if you experience vision changes or have a family history of eye disease. However, finding this variant alone is not a medical emergency or an indication of active illness.
Sources & further reading
Educational information only, last refreshed 9/10/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs61752480?
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 — $29