CHM rs61751242: Understanding the p.Arg293Ter Variant
The rs61751242 variant is a rare, pathogenic nonsense mutation in the CHM gene that introduces a premature stop codon in the encoded protein. This genetic change is associated with Choroideremia, an X-linked inherited disorder characterized by the progressive degeneration of the choroid and retina in males.
What each genotype means
Typical CHM gene sequence
This genotype represents the common, non-variant sequence for this position in the CHM gene. It is not associated with the specific pathogenic nonsense mutation described in clinical literature for this variant.
This is the most common genotype found in the general population.
Heterozygous carrier status
This genotype indicates the presence of the pathogenic rs61751242 variant on one X chromosome. Because the CHM gene is located on the X chromosome, this variant is typically associated with X-linked choroideremia in males, while females are generally asymptomatic carriers due to X-inactivation patterns.
This genotype is extremely rare, with a global minor allele frequency reported at less than 0.00001 in large-scale population databases like gnomAD.
Pathogenic variant present
This genotype indicates the presence of the pathogenic nonsense variant (p.Arg293Ter) on both X chromosomes in females or the hemizygous state in males. This variant leads to a premature stop codon, resulting in defective prenylation of Rab GTPases, which is a known cause of progressive degeneration of the choroid and retina.
This genotype is exceptionally rare in the general population, consistent with its classification as a pathogenic mutation for a rare Mendelian disorder.
What is the rs61751242 Variant?
The rs61751242 variant, often referred to in clinical literature as p.Arg293Ter (or R293X), is a single nucleotide change located within the CHM gene. In genetic terms, this is a nonsense mutation, meaning the DNA sequence alteration creates a stop signal earlier than normal during the process of protein translation. Because this occurs at position 293 of the protein chain, the cell halts production of the Rab escort protein-1 (REP-1) prematurely, resulting in a truncated, non-functional protein. This variant is classified in databases such as ClinVar as pathogenic, as it disrupts the essential biological machinery required for cellular maintenance in the eye. Because CHM is located on the X chromosome, the inheritance pattern is strictly X-linked, meaning the clinical presentation of this variant is observed primarily in males who possess only one X chromosome.
The Role of the CHM Gene
The CHM gene provides the instructions for creating a protein known as Rab escort protein-1 (REP-1). This protein plays a critical role in a cellular process called prenylation, which involves attaching specific molecules to Rab GTPases. Rab proteins are essential traffic controllers within cells, helping to manage the movement and recycling of vesicles—small sacs that transport materials to different parts of the cell. In the context of the eye, particularly within the retinal pigment epithelium and the choroid, this trafficking process is vital for maintaining the health and survival of photoreceptor cells. When the CHM gene is mutated, as in the case of rs61751242, prenylation of Rab proteins is impaired. This defect causes toxic metabolic waste to accumulate or prevents necessary nutrients from reaching these sensitive cells, eventually leading to the characteristic cellular degeneration observed in those affected by the resulting condition.
Research and Clinical Evidence
Scientific research consistently identifies CHM variants, including rs61751242, as direct causes of Choroideremia. Evidence for this association is strong and well-documented in clinical genetics literature, as the loss of REP-1 function is the established molecular mechanism for this disease. Unlike common complex traits—where a variant might only slightly increase the risk of a condition—this variant is considered highly penetrant, meaning individuals carrying this mutation are highly likely to develop symptoms. Research on this specific variant has been documented in various clinical case studies and ocular genetic databases. While the association between this specific genotype and the condition is robust, the progression rate and specific severity of vision loss can sometimes vary between individuals, suggesting that other genetic or environmental factors may influence the clinical course. Clinicians categorize this as a Mendelian, monogenic variant rather than a polygenic risk factor.
What This Means for You
Understanding your genetic status regarding rs61751242 is primarily relevant in the context of diagnostic clinical genetics. If you or a family member have received a report identifying this variant, it is essential to consult with a certified genetic counselor or a specialist in retinal diseases. Because this is a pathogenic variant, it is not a typical risk factor that can be mitigated by lifestyle changes; rather, it provides information about the underlying cause of a specific hereditary condition. This information can be used by clinical professionals to guide family planning, inform reproductive choices, and monitor ocular health. Never use genetic test results to make medical decisions or change treatments without professional clinical supervision. If you have concerns about your vision or genetic history, your primary care physician can provide a referral to the appropriate specialists who can interpret these results in the context of your overall health and family medical history.
How common is this variant?
According to the Genome Aggregation Database (gnomAD), the rs61751242 variant is extremely rare, with a global minor allele frequency of less than 0.00001. It is a classic X-linked null mutation rarely found in the general population.
Frequently asked questions
What is Choroideremia?
Choroideremia is a rare, inherited disorder that causes progressive vision loss, often beginning with night blindness in childhood and progressing to peripheral and central vision loss. It is caused by mutations in the CHM gene, which leads to the degeneration of the light-sensitive tissues in the back of the eye.
Can lifestyle changes prevent issues if I have this variant?
The rs61751242 variant is a pathogenic, structural change in the gene, and there are currently no known lifestyle modifications or supplements that can prevent or reverse the cellular damage it causes. Management of the condition focuses on regular monitoring by ophthalmologists to track vision changes and provide supportive care.
Does this variant affect everyone the same way?
While the variant is highly penetrant, the specific experience of vision loss can vary between individuals. Factors such as the specific genetic background and other modifier genes may influence the exact age of onset or the rate of progression.
Should I get tested for this?
Genetic testing for this variant is typically recommended only if there is a family history of Choroideremia or if a patient exhibits symptoms of retinal degeneration. It is best to discuss the necessity and implications of such testing with a clinical geneticist or your doctor.
Sources & further reading
Educational information only, last refreshed 9/17/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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