SHH rs387906945: Understanding This Rare Genetic Variant
The rs387906945 variant is a rare genetic change located within the SHH gene, which is essential for proper embryonic development. It has been identified in clinical research as a potential factor in conditions involving optic fissure closure defects, such as congenital ocular coloboma.
What each genotype means
Typical risk profile
You carry two copies of the common reference allele at this position in the SHH gene. This genotype is not associated with congenital structural eye anomalies or optic fissure closure defects. It reflects the standard baseline profile observed in the general population.
Carried by more than 99.9% of individuals across all major global populations.
Increased coloboma risk
You carry one copy of the rare pathogenic variant allele at this position in the SHH gene. In clinical databases such as ClinVar, this variant is cataloged with limited evidence linking it to autosomal dominant optic fissure closure defects, including ocular coloboma and microphthalmia. However, phenotypic expression and penetrance can vary, and findings should be evaluated alongside clinical eye evaluations and genetic counseling rather than viewed as an independent diagnosis.
Extremely rare; identified in fewer than 1 in 100,000 individuals globally and often cataloged as an ultra-rare or private family variant.
What is rs387906945?
The identifier rs387906945 refers to a specific single nucleotide polymorphism (SNP) located within the SHH gene. In genetics, a SNP represents a variation at a single position in the DNA sequence. This particular variant is categorized as a rare or private mutation, meaning it is not commonly found in the general population. It is cataloged in clinical databases due to its potential association with structural eye abnormalities. Because it is so rare, much of the current understanding of this variant comes from clinical case studies rather than large-scale population screenings. It sits within the coding region of the SHH gene, which is responsible for producing the Sonic Hedgehog protein, a critical signaling molecule that acts as a blueprint for how various tissues and organs, including the eyes and brain, are shaped during early development.
The Role of the SHH Gene
The SHH gene provides the instructions for creating the Sonic Hedgehog protein. This protein is a fundamental chemical signal that guides the growth and specialization of cells in the developing embryo. It is particularly vital for the 'patterning' of the body, ensuring that structures like the brain and eyes form in their correct locations and sizes. When the SHH gene functions normally, it helps the brain divide into two hemispheres and ensures the eyes develop properly. If the activity of this protein is reduced or eliminated due to a genetic variant, it can lead to developmental issues. These may include holoprosencephaly, where the brain fails to divide, or ocular coloboma, a condition where the tissue of the eye does not close properly during development, leaving a gap or 'cleft' in structures like the iris or retina.
Research and Clinical Evidence
Evidence linking rs387906945 to clinical conditions is currently classified as limited. While the SHH gene is well-documented as a cause for various developmental disorders, specific variants like rs387906945 are often identified in small cohorts or individual clinical cases. Research into ocular coloboma has investigated many candidate genes, including SHH, to understand the genetic basis of these structural defects. Because this variant is extremely rare, it is difficult for researchers to establish a definitive statistical association with the same level of confidence as more common variants. Current clinical databases, such as ClinVar, note its potential pathogenicity, but it remains a subject of ongoing study. It is important to recognize that the presence of a variant does not guarantee a specific health outcome, as many factors, including other genes and environmental influences, contribute to complex developmental processes.
Population Frequency
The rs387906945 variant is considered an ultra-rare or private variant. According to data from large-scale genomic projects like gnomAD, it is not observed at any significant frequency in the general population. This rarity is typical for variants that have a strong impact on early development, as such mutations are often subject to strong selective pressure. Because it is not a common polymorphism, it is not typically included in standard ancestry-based genetic testing panels. Its presence is usually only identified through specialized clinical sequencing performed when a patient presents with specific congenital anomalies. The lack of widespread population data means that we cannot currently describe its frequency across different ancestral groups, as it appears to be restricted to very specific, isolated instances.
Interpreting Genetic Information
If you or a family member have been identified as carrying this variant, it is essential to understand that this information is for educational purposes and does not constitute a medical diagnosis. Genetic variants in developmental genes like SHH are complex, and their clinical significance can vary based on the individual's overall genetic background. You cannot 'treat' or 'change' a genetic variant, but understanding your genetic profile can help you and your healthcare providers make informed decisions about monitoring and care. If you have concerns about ocular health or developmental history, the most appropriate step is to consult with a clinical geneticist or a genetic counselor. These professionals can provide context based on your specific clinical presentation and family history, helping you navigate the implications of genetic findings in a way that is accurate and personalized to your situation.
How common is this variant?
This is an ultra-rare or private variant that is not found at any significant frequency in global population databases like gnomAD.
Frequently asked questions
What is an ocular coloboma?
An ocular coloboma is a congenital condition where a portion of the eye tissue, such as the iris, retina, or optic nerve, is missing or did not close properly during development. It occurs when the embryonic fissure fails to fuse, resulting in a gap in the eye structure.
Is rs387906945 a common genetic variant?
No, rs387906945 is an ultra-rare variant. It is not found in the general population at any significant frequency and is typically only identified in specific clinical contexts.
Can I change my SHH gene sequence?
No, your genetic sequence is inherited and cannot be changed. Genetic information is used to understand health risks and guide clinical care, but it is not something that can be altered through lifestyle or medication.
What should I do if I have this variant?
If you have received a report indicating you carry this variant, you should discuss the findings with a clinical geneticist or a genetic counselor. They can help interpret the result in the context of your personal and family health history.
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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