MYOC rs74315457: Understanding the Gln368STOP Variant
The rs74315457 variant in the MYOC gene, commonly known as Gln368STOP, is a well-studied genetic marker associated with an increased risk of primary open-angle glaucoma (POAG). While it is a recognized factor in some cases of adult-onset glaucoma, its presence does not guarantee the development of the condition.
What each genotype means
Typical myocilin profile
This genotype represents the common, non-variant form of the MYOC gene. It is not associated with the increased risk of primary open-angle glaucoma linked to the Gln368STOP mutation.
This is the most common genotype found in the general population across all ancestries.
Increased glaucoma risk
This genotype contains the Gln368STOP mutation, which is a well-documented risk factor for primary open-angle glaucoma. Research indicates that individuals with this variant have a higher lifetime risk of developing glaucoma, though penetrance is incomplete, meaning not everyone with this genotype will develop the disease. You should discuss regular eye pressure monitoring and comprehensive eye exams with your ophthalmologist.
The minor allele frequency is approximately 0.1% to 0.2% in European ancestry cohorts.
High glaucoma risk
This genotype is homozygous for the Gln368STOP mutation. While rare, this configuration is associated with a significantly increased risk of developing juvenile- or adult-onset primary open-angle glaucoma. It is important to consult with an eye care specialist for routine screening and management of intraocular pressure.
This genotype is extremely rare in the general population.
What is the rs74315457 Variant?
The rs74315457 variant, often referred to in scientific literature as Gln368STOP or p.Gln368Ter, is a specific change in the DNA sequence of the MYOC gene. Located on chromosome 1, this variant acts as a 'stop' signal, causing the cell to produce a truncated, or shortened, version of the myocilin protein. Because this mutation occurs in the olfactomedin domain of the protein—a region critical for its function—it is believed to interfere with the normal behavior of the protein within the eye. This variant is one of many identified in the MYOC gene, but it is particularly notable for its association with glaucoma in various populations. Geneticists track this specific location to better understand how structural changes in proteins can influence long-term ocular health.
The Role of the MYOC Gene
The MYOC gene provides instructions for making a protein called myocilin. This protein is expressed in several parts of the eye, most notably in the trabecular meshwork, which is the drainage system responsible for regulating intraocular pressure. When the drainage system functions correctly, fluid flows out of the eye at a steady rate, maintaining healthy pressure levels. Research suggests that when the MYOC gene is mutated, the resulting abnormal myocilin protein may accumulate within the trabecular meshwork. This accumulation is hypothesized to impede fluid outflow, potentially leading to increased intraocular pressure, a primary risk factor for glaucoma. While the exact mechanism remains a subject of ongoing research, the link between MYOC dysfunction and the disruption of eye pressure regulation is a cornerstone of modern glaucoma genetics.
Research and Clinical Associations
The association between rs74315457 and primary open-angle glaucoma (POAG) has been extensively studied. Research indicates that individuals carrying this variant have a higher statistical risk of developing glaucoma compared to the general population. However, the evidence is nuanced; studies have shown that the penetrance—the proportion of people with the mutation who actually develop the disease—is not absolute. Recent meta-analyses suggest that approximately 1 in 4 individuals with this specific mutation may show clinical evidence of glaucoma. This indicates that while the variant is a significant risk factor, other genetic and environmental factors likely play a role in whether or not an individual develops the condition. Because of this, the variant is considered a 'higher-attention' marker in clinical research rather than a definitive diagnostic tool for the disease.
Population Frequency
The frequency of the rs74315457 variant varies across different ancestral groups. In European ancestry cohorts, the minor allele frequency is generally reported to be between 0.1% and 0.2%. While it has been identified in various populations worldwide, its prevalence is relatively low, making it a rare variant in the general population. Some studies have noted that the mutation is more frequently observed in specific clinical cohorts of glaucoma patients, though its absence in other groups, such as certain Asian populations, has also been documented. These variations highlight the importance of considering ancestral background when interpreting genetic risk factors, as the impact and frequency of specific variants can differ significantly depending on the population being studied.
What This Information Means for You
Understanding your genetic status regarding rs74315457 is a matter of assessing statistical risk rather than receiving a medical diagnosis. If you have been informed that you carry this variant, it does not mean you will inevitably develop glaucoma. Conversely, not having this variant does not eliminate the risk of developing the condition, as glaucoma is a complex, multifactorial disease influenced by many genes and environmental factors. This information should be used as a tool to facilitate informed conversations with your eye care professional. If you are concerned about your ocular health, the most effective step is to schedule regular, comprehensive eye examinations. Always consult with an ophthalmologist or a genetic counselor to interpret your results in the context of your personal and family medical history. Never make changes to your health management or medication based solely on genetic data without professional guidance.
How common is this variant?
The rs74315457 variant is rare, with a minor allele frequency of approximately 0.1-0.2% in European ancestry cohorts.
Frequently asked questions
Does having the rs74315457 variant mean I will get glaucoma?
No, having this variant does not guarantee you will develop glaucoma. It is a risk factor, but research shows that only a portion of individuals with this mutation go on to develop the disease.
What should I do if I have the MYOC Gln368STOP mutation?
If you are aware that you carry this variant, you should discuss it with your eye care professional. They can provide personalized advice on how often you should have your eye pressure and optic nerve health monitored.
Is this the only gene associated with glaucoma?
No, glaucoma is a complex condition associated with many different genes and environmental factors. MYOC is just one of several genes that have been linked to the development of the disease.
Can I prevent glaucoma if I have this genetic variant?
While you cannot change your genetics, regular eye exams are the best way to detect early signs of glaucoma. Early detection allows for timely management, which can help preserve your vision.
Sources & further reading
Educational information only, last refreshed 9/28/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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A major missense variant in the myocilin olfactomedin domain causative of juvenile- and adult-onset primary open-angle glaucoma.
Missense mutation in MYOC (p.Gln368Glu) predisposing carriers to elevated intraocular pressure and adult-onset primary open-angle glaucoma.
A pathogenic point mutation in MYOC strongly linked to autosomal dominant primary open-angle glaucoma with high intraocular pressure.
A pathogenic missense variant in myocilin causing trabecular meshwork disruption and juvenile-onset open-angle glaucoma.
Known as the Gln368STOP mutation in MYOC, this nonsense variant is a well-established cause of autosomal dominant juvenile- and adult-onset primary open-angle glaucoma.
A pathogenic missense variant (p.Gln368Ter) in the MYOC gene, a major genetic risk factor for primary open-angle glaucoma.