CFTR rs113993966: Understanding the p.Arg117His Variant
The rs113993966 variant in the CFTR gene, commonly referred to as p.Arg117His (R117H), is a well-documented genetic alteration associated with a spectrum of CFTR-related disorders. Its clinical impact is significantly modulated by other genetic factors, specifically the length of the poly-T tract located in the same gene.
What each genotype means
Typical CFTR Function
You carry two reference copies of the CFTR gene at position c.350, showing no presence of the R117H missense alteration. This genotype does not confer an elevated inherited risk for CFTR-related disorders or variable-expressivity cystic fibrosis at this locus. Typical population carrier risks for other CFTR variants elsewhere in the gene may still apply.
Found in more than 99.4% of individuals globally, including approximately 99.4% to 99.7% of individuals of European descent.
CFTR Variant Carrier
You carry one copy of the c.350G>A (p.Arg117His or R117H) variant, designating you as a carrier of an allele associated with variable-expressivity CFTR conditions. Carrier status alone typically does not cause classical cystic fibrosis, but clinical expressivity can vary depending on what CFTR variants exist on the other chromosome and nearby poly-T/TG splice tract variants (such as 5T or 7T) on the same chromosome. Genetic counseling and carrier screening are commonly considered for family planning.
Carried by approximately 1 in 300 to 1 in 350 individuals of European ancestry (~0.3%), but is substantially rarer in East Asian and African populations.
Variable CFTR Risk
You carry two copies of the R117H (p.Arg117His) alteration in the CFTR gene. Published studies indicate this genotype is linked to a variable clinical spectrum ranging from asymptomatic status to CFTR-related disorders such as congenital bilateral absence of the vas deferens (CBAVD) or mild cystic fibrosis, strongly modulated by the co-inherited poly-T splice tract variants (5T, 7T, or 9T). Comprehensive clinical evaluation and genetic counseling are recommended to interpret individual clinical context.
Extremely rare across all populations, occurring in fewer than 1 in 100,000 individuals globally.
What is the rs113993966 Variant?
The rs113993966 variant, technically identified as c.350G>A, results in the substitution of the amino acid arginine with histidine at position 117 of the CFTR protein. This variant is located within the CFTR gene, which provides instructions for making the cystic fibrosis transmembrane conductance regulator protein. This protein functions as a channel that transports negatively charged particles called chloride ions into and out of cells. The movement of chloride ions helps control the movement of water in tissues, which is necessary for the production of thin, freely flowing mucus. When this protein is dysfunctional, it can lead to the production of thick, sticky mucus that clogs airways and ducts in various organs.
Clinical Associations and Evidence
Research indicates that the R117H variant is associated with a broad phenotypic spectrum, ranging from individuals who are clinically asymptomatic to those with congenital bilateral absence of the vas deferens (CBAVD) or non-classic cystic fibrosis. The evidence for its pathogenicity is well-established, but the severity of the condition is not determined by this variant alone. Instead, it is heavily influenced by the poly-T tract and TG repeats located in intron 8 of the CFTR gene. For example, when R117H is found in cis (on the same chromosome) with a 5T allele, it is generally considered a more significant risk factor for CFTR-related disorders compared to when it is paired with a 7T allele. Because of this complexity, clinical interpretation requires careful consideration of the entire genetic context.
Population Frequency
The frequency of the rs113993966 variant varies significantly across different ethnic and geographic populations. It is considered a rare variant in the general population, though it has been identified with higher frequency in certain groups of European descent. Because it is a rare variant, most individuals do not carry it. Genetic screening programs often include this variant due to its known association with CFTR-related conditions, but the prevalence of the carrier state is low enough that it is not considered a common polymorphism in the general population.
Navigating Genetic Information
Understanding your genetic status regarding rs113993966 is a complex process that should be handled with the guidance of a qualified healthcare professional or a genetic counselor. This information cannot be used to diagnose a condition or predict a specific health outcome on its own. Because the clinical expression of this variant is modulated by other genetic factors like the poly-T tract, a simple test result is often insufficient for a complete clinical picture. If you have received information about this variant, you should discuss the findings with your clinician. They can help interpret the results in the context of your personal and family medical history and determine if further testing or clinical evaluation is appropriate for your specific situation.
How common is this variant?
The rs113993966 variant is rare, with carrier frequency varying significantly by ethnicity and geographic origin.
Frequently asked questions
Is rs113993966 the same as R117H?
Yes, rs113993966 is the unique identifier (rsID) used in scientific databases to refer to the specific genetic change known as p.Arg117His or R117H in the CFTR gene.
Does having the R117H variant mean I have cystic fibrosis?
Not necessarily. The R117H variant is associated with a wide spectrum of outcomes, ranging from no symptoms to mild CFTR-related disorders. Clinical expression depends on other genetic factors, such as the poly-T tract length.
What is the role of the poly-T tract?
The poly-T tract is a sequence in the CFTR gene that influences how the gene is processed. It modulates the severity of the R117H variant by affecting how much functional CFTR protein is produced.
Should I be tested for this variant?
Genetic testing decisions should be made in consultation with a healthcare provider or genetic counselor. They can determine if testing is relevant based on your family history or clinical symptoms.
Sources & further reading
Educational information only, last refreshed 10/5/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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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.
Also known as p.Arg117His (R117H), this CFTR variant is associated with mild or atypical cystic fibrosis and congenital bilateral absence of the vas deferens, with clinical severity influenced by the poly-T tract background.
A CFTR mutation associated with cystic fibrosis and CFTR-related disorders.