CFTR rs121908744: Understanding the p.Arg117His Variant
The rs121908744 variant in the CFTR gene, commonly known as p.Arg117His, is a genetic change associated with variable clinical outcomes, including mild cystic fibrosis or congenital bilateral absence of the vas deferens. Its impact depends heavily on the presence of other genetic factors, such as specific polythymidine tracts within the CFTR gene.
What each genotype means
Typical CFTR function
This genotype represents the common, non-variant sequence at this position in the CFTR gene. It is not associated with the specific risks of cystic fibrosis or congenital bilateral absence of the vas deferens linked to the R117H variant.
This is the most common genotype found in the vast majority of the global population.
R117H carrier status
This genotype indicates you carry one copy of the R117H variant (c.350G>A). The clinical impact of this variant is variable and often depends on other genetic factors, such as the length of the poly-T tract in the CFTR gene; individuals with this variant should consult a genetic counselor or clinician to discuss the need for additional testing to determine accurate risk.
Carried by roughly 1 in 333 people (0.003) of European ancestry; frequency varies significantly across other global populations.
R117H homozygous status
This genotype indicates you carry two copies of the R117H variant. This variant is known for variable penetrance and expressivity, meaning it can be associated with mild cystic fibrosis or congenital bilateral absence of the vas deferens, especially when influenced by other genetic modifiers like the poly-T tract. You should discuss these results with a medical professional or genetic specialist to understand your specific clinical implications.
This genotype is very rare in the general population.
What is rs121908744?
The variant rs121908744, often referred to by its protein change p.Arg117His (or R117H), is a specific alteration in the DNA sequence of the CFTR gene located on chromosome 7. In this variant, the amino acid arginine is replaced by histidine at position 117 of the CFTR protein. This change is classified as a missense variant, meaning it alters the genetic code to produce a protein with a different amino acid. Because the CFTR gene is responsible for creating a protein that regulates the movement of salt and water in and out of cells, changes to this protein can affect various organ systems. This specific variant is notable for its variable penetrance, meaning that individuals who carry it may experience a wide range of health outcomes, or in some cases, no symptoms at all, depending on their overall genetic background.
The Role of the CFTR Gene
The CFTR gene provides instructions for making the cystic fibrosis transmembrane conductance regulator protein. This protein functions as a channel across the membrane of cells that produce mucus, sweat, saliva, tears, and digestive enzymes. By controlling the flow of chloride ions, the CFTR protein helps maintain the balance of salt and water on cell surfaces, which is essential for the normal function of organs like the lungs, pancreas, and reproductive tract. When the CFTR gene contains pathogenic variants, the resulting protein may be absent, non-functional, or have reduced activity. This leads to the production of thick, sticky mucus that can clog airways and ducts. The p.Arg117His variant is considered to have residual function, which is why it is often associated with milder clinical presentations compared to variants that result in a complete loss of protein function.
Research and Clinical Associations
Research indicates that the clinical impact of p.Arg117His is highly dependent on the genetic context in which it occurs. Specifically, the variant is often studied alongside the polythymidine (poly-T) tract in intron 8 of the CFTR gene. The length of this tract (typically 5T, 7T, or 9T) influences how much functional protein is produced. When p.Arg117His is paired with a 5T tract, the combined effect can lead to reduced protein function, potentially resulting in a CFTR-related disorder or mild cystic fibrosis. Because of this complexity, clinical databases like CFTR2 and CFTR-France have sometimes categorized the variant differently, reflecting the difficulty in predicting an individual's health status based on this single variant alone. It is not a simple 'on-off' switch for disease, but rather a factor that contributes to a spectrum of potential clinical outcomes.
Population Frequency
The p.Arg117His variant is relatively rare in the general population, with an estimated frequency of approximately 0.003 in European populations. Because it is a rare variant, it is not commonly found in the general public, and its presence is usually identified through targeted carrier screening or diagnostic testing for cystic fibrosis-related symptoms. The frequency can vary significantly across different ancestral groups, and because it is often associated with milder or late-onset conditions, it may be under-reported in some populations. Genetic counselors and medical professionals use this frequency data to help interpret the significance of the variant when it is identified in a patient, always emphasizing that population statistics do not predict the health of any specific individual.
What This Information Means for You
If you have been informed that you carry the rs121908744 variant, it is important to understand that this does not constitute a medical diagnosis. Genetic variants like p.Arg117His interact with your entire genetic profile, including other variants in the CFTR gene and environmental factors. This information is best used in consultation with a healthcare provider or a certified genetic counselor who can interpret the results in the context of your personal and family medical history. You cannot determine your health risk based on this variant alone. If you are concerned about your carrier status or potential health implications, discuss these findings with your clinician. They can provide appropriate guidance, recommend further testing if necessary, and help you understand what this means for you and your family members.
How common is this variant?
The rs121908744 variant has an estimated frequency of 0.003 in European populations, making it a relatively rare genetic finding.
Frequently asked questions
Is rs121908744 the same as cystic fibrosis?
No, rs121908744 is a specific variant in the CFTR gene. While it is associated with CFTR-related disorders, having this variant does not automatically mean an individual has cystic fibrosis.
What does 'variable penetrance' mean for this variant?
Variable penetrance means that individuals with the same genetic variant may show different symptoms or no symptoms at all. This occurs because other genetic and environmental factors influence how the variant affects the body.
Should I be worried if I have this variant?
Finding a variant does not mean you have a disease. You should discuss your results with a genetic counselor or physician who can explain the findings in the context of your overall health.
How is this variant tested?
This variant is typically identified through clinical genetic testing, such as carrier screening or diagnostic panels for cystic fibrosis. These tests are usually ordered by a healthcare provider.
Sources & further reading
Educational information only, last refreshed 9/23/2026. 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.