PAX6 rs121907925: What Your Genotype Means
The rs121907925 variant is a rare, pathogenic genetic change located within the PAX6 gene. It is clinically associated with developmental eye conditions, specifically congenital ocular coloboma and optic disc malformations.
What each genotype means
Typical ocular development risk
You carry two reference copies of this position in the PAX6 gene. This genotype is not associated with PAX6-related congenital ocular malformations such as aniridia or coloboma.
Carried by virtually 100% of individuals across all major global populations in gnomAD.
High risk for ocular malformations
You carry one copy of the pathogenic missense variant in PAX6. In published medical genetics literature, heterozygous carriers are at high risk for developmental eye disorders, including iris hypoplasia, aniridia, or congenital ocular coloboma.
Extremely rare; observed in fewer than 1 in 100,000 individuals globally and absent from most population databases.
Severe developmental anomaly risk
Carrying two copies of this pathogenic variant is exceptionally rare and represents homozygous PAX6 disruption. Biallelic PAX6 mutations are typically associated with severe, complex congenital malformations affecting eye and neural development.
Extremely rare to near-zero globally, documented primarily in rare consanguineous pedigrees.
Understanding the Variant
The variant rs121907925 is a specific change in the DNA sequence of the PAX6 gene, located on chromosome 11. In genetic databases, this variant is identified by its rsID, which serves as a unique label for researchers and clinicians. This particular variant is classified as a missense mutation, meaning it results in a single amino acid substitution within the protein produced by the gene. Because the PAX6 gene is highly sensitive to changes in its structure and dosage, even small alterations can have significant impacts on how the protein functions during the critical stages of embryonic development. This variant is documented in clinical databases like ClinVar as being pathogenic, meaning it is linked to specific developmental health conditions rather than being a benign variation found in the general population.
The Role of the PAX6 Gene
The PAX6 gene acts as a master regulator, often described as a transcription factor, which means it controls the activity of many other genes. It is essential for the proper development of the eyes, brain, and central nervous system. During early development, PAX6 provides the instructions necessary for the formation of various ocular structures, including the iris, the retina, and the optic nerve. Because it is a 'dosage-sensitive' gene, the body requires a precise amount of functional PAX6 protein to ensure that eye development proceeds correctly. When a mutation occurs, it can lead to either a loss of function or an altered function of the protein. This disruption prevents the gene from effectively coordinating the complex biological processes required to build a healthy eye, which can lead to a spectrum of congenital eye malformations.
Clinical Associations and Evidence
Research associates the rs121907925 variant with congenital ocular coloboma and coloboma of the optic disc. A coloboma is a gap or split in one of the structures of the eye, such as the iris or the optic nerve, which occurs when the eye does not close completely during fetal development. While many PAX6 mutations are famously linked to aniridia (the absence of the iris), missense variants like rs121907925 are more frequently associated with non-aniridia phenotypes, such as isolated foveal hypoplasia or optic nerve anomalies. The evidence for this variant's pathogenicity is derived from clinical observations of individuals presenting with these specific ocular malformations. It is important to note that while the association with these conditions is established in clinical literature, the exact severity and range of symptoms can vary significantly between individuals, even those who may carry the same genetic variant.
Population Frequency
The rs121907925 variant is extremely rare. It is essentially absent or found at near-zero frequencies in large-scale population databases like gnomAD, which aggregate genetic data from diverse global populations. Because it is not a common polymorphism, it is not typically found in the general population and is instead identified primarily in clinical settings through targeted genetic testing of individuals who have already been diagnosed with specific ocular developmental issues. Its rarity underscores that this is not a common variation that one would expect to find in a healthy, asymptomatic individual. If this variant is identified in a clinical report, it is usually because it was investigated as a potential explanation for a known, pre-existing medical condition.
What This Information Means for You
If you or a family member have received information regarding this variant, it is essential to understand that this is a clinical finding, not a lifestyle or wellness marker. Genetic variants in PAX6 are associated with serious developmental conditions that require specialized care. This information should not be used for self-diagnosis or to make medical decisions. If you have concerns about your vision or a family history of ocular malformations, the most appropriate step is to consult with a medical geneticist or a specialized ophthalmologist. These professionals can provide context based on your specific clinical history, perform necessary diagnostic testing, and offer guidance on management or support. Never attempt to interpret clinical genetic reports without the assistance of a qualified healthcare provider who can explain the findings in the context of your overall health.
How common is this variant?
This variant is extremely rare and is considered absent or near-zero in global populations according to gnomAD data.
Frequently asked questions
Is rs121907925 a common genetic variant?
No, this variant is extremely rare. It is not found in the general population and is typically only identified in clinical settings during the investigation of specific eye conditions.
What conditions are linked to PAX6 variants?
PAX6 variants are associated with a range of developmental eye disorders, including aniridia, congenital ocular coloboma, foveal hypoplasia, and cataracts. These conditions affect the structure and function of the eye from birth.
Can I use this information to diagnose myself?
No. Genetic information regarding pathogenic variants must be interpreted by a qualified medical professional. You should discuss any genetic findings with a genetic counselor or ophthalmologist.
What should I do if I have this variant?
If you have been identified as a carrier of this variant, you should consult with a medical geneticist or an ophthalmologist. They can provide a clinical evaluation and discuss what this means for your eye health.
Sources & further reading
Educational information only, last refreshed 10/18/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs121907925?
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 PAX6
Pathogenic loss-of-function nonsense variant in PAX6 resulting in congenital absence of the iris (aniridia) and associated anterior segment dysgenesis.
A high-penetrance single nucleotide substitution disrupting PAX6 function and leading to aniridia and congenital anterior segment dysgenesis.
Nonsense change in PAX6 leading to haploinsufficiency and classical congenital aniridia.
A classic nonsense mutation (p.Arg240Ter) in the PAX6 master regulator of eye development leading to haploinsufficiency and congenital aniridia.
Intronic regulatory polymorphism in the ocular master regulator PAX6 associated with axial length variation and myopia development.
Classical stop-gain variant in PAX6 leading to haploinsufficiency and congenital aniridia with associated foveal hypoplasia and decreased visual acuity.