CFTR rs5030933: Understanding the R117H Variant
The rs5030933 variant, commonly known as p.Arg117His or R117H, is a genetic change in the CFTR gene. It is associated with a spectrum of clinical outcomes, ranging from asymptomatic states to mild or atypical forms of cystic fibrosis and congenital bilateral absence of the vas deferens (CBAVD).
What each genotype means
Typical CFTR Function
You carry two copies of the common G allele, coding for the standard arginine at position 117 of the CFTR protein. This genotype is not associated with the p.Arg117His variant or CFTR-related disorders linked to this position. However, it does not rule out carrier status for other unrelated variations across the CFTR gene.
Carried by more than 99% of people across most global populations, including European ancestries.
Carrier of CFTR R117H
You carry one copy of the A allele, corresponding to the p.Arg117His (R117H) variant in the CFTR gene. Carrying a single copy generally does not cause cystic fibrosis on its own, but clinical outcomes depend strongly on whether another CF-causing mutation is present on the opposite chromosome and the length of the poly-T tract (such as 5T or 7T) located on the same chromosome. Individuals with this genotype are considered carriers and may show variable penetrance ranging from no symptoms to mild CFTR-related conditions like congenital bilateral absence of the vas deferens (CBAVD) or late-onset atypical symptoms if paired with another pathogenic variant.
Found in approximately 1 in 150 to 1 in 200 individuals of European descent, and significantly rarer in East Asian and African populations.
Biallelic CFTR R117H
You carry two copies of the A allele, indicating homozygosity for the p.Arg117His (R117H) alteration. Research shows this genotype is associated with variable CFTR dysfunction that is heavily modulated by the background poly-thymidine (poly-T) tract length on each chromosome. Manifestations can range from asymptomatic status to mild or atypical CFTR-related conditions, including congenital bilateral absence of the vas deferens (CBAVD) in males and variable pulmonary or pancreatic involvement.
Extremely rare across all global ancestries, estimated to occur in fewer than 1 in 100,000 individuals.
What is the rs5030933 Variant?
The rs5030933 variant, technically identified as c.350G>A, is a single nucleotide polymorphism located in exon 4 of the CFTR gene. This specific change results in the substitution of the amino acid arginine with histidine at position 117 of the CFTR protein. Because this alteration occurs within the transmembrane region of the protein, it can affect the function of the CFTR channel. Research indicates that while the protein is still produced, its ability to transport chloride ions is reduced compared to the wild-type protein. This variant is not a simple 'on-off' switch for disease; rather, it is classified as a Class IV mutation, meaning it allows for some residual channel function. Consequently, the clinical impact of this variant is highly variable and often depends on other genetic factors present in an individual's DNA.
The Role of the CFTR Gene
The CFTR gene provides instructions for creating the cystic fibrosis transmembrane conductance regulator protein. This protein functions as a channel across the membranes of cells that produce mucus, sweat, saliva, tears, and digestive enzymes. By transporting negatively charged chloride ions into and out of cells, the CFTR protein helps control the movement of water in tissues, which is necessary for the production of thin, freely flowing mucus. When the CFTR protein is dysfunctional, mucus becomes thick and sticky, which can clog airways and ducts in the lungs, pancreas, and reproductive system. Because R117H retains some residual function, it typically does not cause the severe, classic form of cystic fibrosis seen with more disruptive mutations, but it can still lead to CFTR-related disorders, particularly when paired with other genetic modifiers.
Clinical Associations and the Poly-T Tract
The clinical severity associated with R117H is famously modulated by a nearby genetic feature known as the poly-T tract, located in intron 8 of the CFTR gene. This tract consists of a series of thymine bases (5T, 7T, or 9T) that influence how the gene is spliced. The 5T allele is particularly significant because it reduces the efficiency of splicing, leading to lower levels of functional CFTR protein. When R117H is inherited on the same chromosome as a 5T allele (in cis), the combined effect often results in more significant clinical symptoms, such as CBAVD or atypical cystic fibrosis. Conversely, if R117H is paired with a 7T or 9T allele, the phenotype is generally much milder. Because of this complex interplay, clinicians often test for both the R117H variant and the poly-T tract status to better understand an individual's specific risk profile.
Population Frequency
The R117H variant is relatively rare in the general population. Its minor allele frequency is approximately 0.003 across global populations, though it is observed more frequently in individuals of European ancestry, where the frequency is approximately 0.005. Because it is a rare variant, most individuals do not carry it. However, in specific populations or families where the variant is more common, genetic counseling is often recommended to help interpret the potential health implications. It is important to note that population frequency data provides a broad overview and does not predict the specific health status of any single individual. Genetic testing results should always be interpreted in the context of a person's full clinical history and family background by a qualified healthcare professional.
Navigating Genetic Information
Understanding your genetic status for rs5030933 requires careful interpretation. If you have received results indicating you carry this variant, it is essential to discuss the findings with a genetic counselor or a physician who specializes in genetics. They can help explain what this means for you or your family, especially regarding the potential for CFTR-related disorders. You cannot use this information to self-diagnose or predict future health outcomes with certainty, as the clinical expression of this variant is highly dependent on other genetic modifiers like the poly-T tract. If you are concerned about symptoms or family history, a clinical evaluation is the only way to obtain an accurate assessment. Always rely on professional medical guidance rather than online databases when making decisions about your health or reproductive planning.
How common is this variant?
The minor allele frequency of rs5030933 is approximately 0.003 globally, with a slightly higher frequency of about 0.005 in European-ancestry populations.
Frequently asked questions
Is R117H the same as having cystic fibrosis?
Not necessarily. R117H is a variant associated with a spectrum of outcomes, including atypical or mild forms of cystic fibrosis and CFTR-related disorders like CBAVD, but it does not automatically result in a diagnosis of classic cystic fibrosis.
What is the poly-T tract and why does it matter?
The poly-T tract is a sequence of thymine bases in the CFTR gene that affects how the gene is processed. It acts as a modifier; for example, a 5T allele can make the R117H variant more likely to cause symptoms by further reducing functional protein levels.
Can I be a carrier of R117H?
Yes, if you have one copy of the R117H variant (a GA genotype), you are considered a carrier. Carriers are generally healthy but should consult a genetic counselor if they are concerned about the risk of passing the variant to their children.
Should I get tested for the poly-T tract if I have R117H?
Clinical guidelines often suggest that individuals who test positive for R117H should also be tested for the poly-T tract. This additional information is crucial for clinicians to provide a more accurate assessment of potential health risks.
Sources & further reading
Educational information only, last refreshed 10/13/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs5030933?
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 CFTR
Severe pathogenic mutation (p.Gly542Ter) associated with cystic fibrosis.
Classic cystic fibrosis in-frame 3-bp deletion variant (p.Phe508del / deltaF508) causing misfolding and impaired chloride channel trafficking.
Pathogenic frameshift mutation (c.3659delC) in CFTR linked to cystic fibrosis.
Pathogenic nonsense variant (p.Gly542Ter / G542X) causing autosomal recessive cystic fibrosis when inherited in trans with another CFTR pathogenic allele.
A CFTR mutation associated with cystic fibrosis and CFTR-related disorders.
A pathogenic variant (p.Arg117His) in the CFTR gene associated with CFTR-related disorders.