RHO rs61748899: What Your Genotype Means
The rs61748899 single nucleotide polymorphism is an extremely rare missense substitution in the rhodopsin (RHO) gene on chromosome 3. It results in an amino acid change known as p.Pro347Leu, altering a critical structural site near the C-terminus of the rhodopsin protein. In clinical genetic databases and published ophthalmology literature, this alteration is identified as a pathogenic driver of autosomal dominant retinitis pigmentosa, leading to progressive rod photoreceptor degeneration and early night blindness.
What each genotype means
Typical rhodopsin function
You carry two copies of the common reference allele at this position, indicating standard rhodopsin protein structure and trafficking. Research shows this genotype is not linked to autosomal dominant retinitis pigmentosa caused by the p.Pro347Leu alteration. It confers a standard baseline visual profile regarding this specific genetic marker.
Carried by more than 99.99% of individuals across all global reference populations.
Increased retinitis pigmentosa risk
You carry one copy of the pathogenic missense variant corresponding to p.Pro347Leu in the RHO gene. Published clinical genetic studies consistently associate this single altered copy with autosomal dominant retinitis pigmentosa, characterized by progressive rod photoreceptor degeneration and early night blindness. Retinal specialists evaluate individual presentation using detailed clinical exams and electroretinography.
Extremely rare worldwide, with an overall population frequency estimated at less than 1 in 100,000 individuals.
Increased retinitis pigmentosa risk
You carry two copies of the altered allele encoding the p.Pro347Leu missense change. Because RHO-associated retinitis pigmentosa follows an autosomal dominant inheritance pattern, carrying either one or two copies is strongly associated with severe progressive photoreceptor degeneration. Homozygous individuals are exceedingly rare in clinical literature and general population databases.
Exceedingly rare across all ancestral populations, essentially unobserved in general reference datasets like gnomAD.
Genetic Architecture and Molecular Location
The variant rs61748899 is located within the RHO gene on human chromosome 3. At the nucleotide level, it typically represents a transition from cytosine to thymine (c.1040C>T), leading to the substitution of a proline residue with a leucine at codon 347 (p.Pro347Leu). The rhodopsin gene encodes a highly specialized G protein-coupled receptor found in the disc membranes of rod photoreceptors in the retina. Proline 347 sits within the cytoplasmic C-terminal tail of the protein, which contains critical transport and sorting signals necessary for moving rhodopsin from the inner segment to the outer segment of photoreceptor cells. Altering this evolutionary conserved proline disrupts the conformational motifs needed for proper vesicular trafficking, contributing to structural cellular stress and accelerated apoptotic pathways within rod cells.
Biological Role and Clinical Evidence
Retinitis pigmentosa (RP) encompasses a group of inherited retinal dystrophies characterized by progressive loss of photoreceptors. Autosomal dominant retinitis pigmentosa caused by mutations in RHO is one of the most thoroughly investigated monogenic retinal conditions. While cataloged under 'limited' evidence in specific high-throughput frameworks, primary clinical repositories like ClinVar consistently evaluate the c.1040C>T (p.Pro347Leu) change as pathogenic or likely pathogenic with established pedigree segregation and functional validation. Multiple independent amino acid substitutions at this precise residue (such as p.Pro347Ser and p.Pro347Ala) also trigger severe, dominant retinal disease. The classic clinical presentation associated with rhodopsin C-terminal mutations includes early childhood or adolescent nyctalopia (night blindness), followed by progressive mid-peripheral visual field loss and gradual constriction toward tunnel vision.
Population Prevalence and Allele Frequency
Across broad multi-ancestry population datasets such as the Genome Aggregation Database (gnomAD), the alternative T allele at rs61748899 is exceptionally rare, registering an allele frequency well below 0.00001 (less than 0.001%). Because RHO-associated retinitis pigmentosa inherited in a dominant pattern is typically penetrant, pathogenic missense variants are strongly selected against in the general population. As a result, the vast majority of individuals across all ancestral backgrounds carry two copies of the ancestral C allele. The presence of the variant allele is almost exclusively detected within individuals or families undergoing diagnostic genomic sequencing for confirmed rod-cone dystrophies rather than in unselected population screening cohorts.
Interpreting Results and Clinical Perspective
Direct-to-consumer genetic screening or research genotyping arrays frequently encounter technical limitations, including false-positive calls when probing extremely rare pathogenic single nucleotide variants. A reported non-reference genotype on an unvalidated consumer test should never be taken as a definitive clinical diagnosis. True confirmation requires dedicated clinical-grade molecular testing, such as targeted Sanger sequencing or next-generation sequencing performed in an accredited laboratory, accompanied by comprehensive clinical evaluation by an ophthalmologist or retinal specialist. Furthermore, this genetic variant cannot be addressed by unsupervised medical adjustments or lifestyle changes alone; any therapeutic options, monitoring regimens, or genetic counseling should be guided directly by qualified medical professionals.
How common is this variant?
The variant allele at rs61748899 is exceptionally rare, observed at an allele frequency of less than 0.00001 across all populations in the Genome Aggregation Database (gnomAD).
Frequently asked questions
What is RHO rs61748899?
RHO rs61748899 is a rare missense mutation in the rhodopsin gene that changes the amino acid proline to leucine at position 347 (p.Pro347Leu). This mutation alters the cytoplasmic tail of the light-sensing rhodopsin protein.
What medical condition is linked to this variant?
This variant is clinically recognized as a cause of autosomal dominant retinitis pigmentosa. Affected individuals typically experience night blindness during youth followed by gradual peripheral visual field reduction.
Is having one copy of the variant enough to cause symptoms?
Yes, retinitis pigmentosa associated with the p.Pro347Leu mutation follows an autosomal dominant inheritance pattern. This means carrying a single altered allele (the CT genotype) is generally sufficient to produce retinal degeneration.
What should I do if a direct-to-consumer DNA test lists this variant?
Raw data from consumer tests can exhibit false positives for ultra-rare variants. You should review the finding with a genetic counselor or retinal specialist to determine if clinical-grade confirmatory testing and an eye examination are appropriate.
Sources & further reading
Educational information only, last refreshed 9/14/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Pathogenic missense variant causing rhodopsin Pro23His substitution that leads to autosomal dominant retinitis pigmentosa and progressive night blindness.
Constitutively active rhodopsin variant (Gly90Asp) causing autosomal dominant congenital stationary night blindness (CSNB).
Encodes the Pro23His (P23H) substitution in rhodopsin, the most common autosomal dominant retinitis pigmentosa allele in North America.
A non-synonymous variant altering rhodopsin protein structure that causes autosomal dominant retinitis pigmentosa with progressive rod photoreceptor loss.
Rhodopsin missense variant (p.Pro23His) responsible for classical autosomal dominant retinitis pigmentosa with rod photoreceptor degeneration.
Classic Pro23His (p.P23H) mutation in rhodopsin causing autosomal dominant retinitis pigmentosa.