CFTR rs121908745: Understanding the p.Arg553Ter Variant
The rs121908745 variant is a specific genetic change located within the CFTR gene. It is classified as a pathogenic nonsense variant, known as p.Arg553Ter, and is frequently monitored in clinical carrier screening for cystic fibrosis.
What each genotype means
Typical CFTR genotype
This genotype represents the common, non-pathogenic sequence at this position in the CFTR gene. It is not associated with the p.Arg553Ter variant and does not indicate carrier status for this specific mutation.
This is the most common genotype observed in the general population across all ancestries.
Cystic fibrosis carrier status
This genotype indicates you carry one copy of the p.Arg553Ter pathogenic variant in the CFTR gene. Carriers are typically asymptomatic, but you should discuss this result with a genetic counselor or clinician to understand the implications for family planning and the potential risk of passing this variant to offspring.
This genotype is rare, with the variant allele occurring at a global frequency of approximately 0.0003 in European non-Finnish populations.
Potential cystic fibrosis risk
This genotype indicates you carry two copies of the p.Arg553Ter pathogenic variant. This variant is classified as pathogenic and is associated with cystic fibrosis, a condition that requires clinical management and specialized care. Please consult with a medical professional or a specialist in cystic fibrosis to discuss these findings and your health status.
This genotype is extremely rare in the general population.
What is the rs121908745 Variant?
The rs121908745 variant is a single nucleotide change in the CFTR gene, specifically identified as c.1657C>T. This change results in a premature stop codon, often referred to as p.Arg553Ter. In genetics, a nonsense variant like this creates a 'stop' signal that tells the cell to stop building the protein before it is finished. Because the resulting protein is truncated, it is typically non-functional or unstable. This variant is located on chromosome 7 and is well-documented in clinical databases like ClinVar. It is considered a significant finding in the context of genetic testing because it disrupts the normal production of the CFTR protein, which is essential for various bodily functions.
The Role of the CFTR Gene
The CFTR gene provides the 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. Its primary job is to transport negatively charged particles called chloride ions into and out of cells. This movement of chloride ions helps control the movement of water in tissues, which is necessary for the production of thin, freely flowing mucus. When the CFTR gene is mutated, the chloride channels do not function correctly, leading to the production of thick, sticky mucus that can clog airways and ducts in the lungs, pancreas, and other organs, which is the hallmark of cystic fibrosis.
Clinical Significance and Research
Research has established that pathogenic variants in the CFTR gene are the underlying cause of cystic fibrosis. The p.Arg553Ter variant is recognized as a severe, disease-causing mutation. Because cystic fibrosis is an autosomal recessive condition, an individual typically needs to inherit two pathogenic variants—one from each parent—to manifest the clinical symptoms of the disease. Individuals who carry only one copy of this variant are generally considered 'carriers.' Carriers usually do not show symptoms of cystic fibrosis, but they have a chance of passing the variant to their children. Clinical guidelines, such as those from the American College of Medical Genetics and Genomics (ACMG), recommend offering CFTR carrier screening to individuals planning a pregnancy to help them understand their reproductive risks.
Population Frequency
The rs121908745 variant is relatively rare in the general population. According to data from the Genome Aggregation Database (gnomAD), the global allele frequency is approximately 0.0003 in European non-Finnish populations. This low frequency indicates that the variant is not common in the general public. Because it is a rare variant, most people will not carry it. However, because it is a known pathogenic variant, it is specifically included in many targeted carrier screening panels used by healthcare providers. These panels are designed to identify individuals who may be at risk of having a child with cystic fibrosis, allowing for informed family planning and early medical consultation.
What This Information Means for You
If you have received information about this variant from a genetic test, it is important to understand that this is not a medical diagnosis. A carrier result simply means you have one copy of a variant that, if paired with another pathogenic variant from your partner, could result in a child with cystic fibrosis. You cannot 'treat' or 'change' your genetic variant. If you are concerned about your carrier status or family planning, the most appropriate step is to discuss your results with a certified genetic counselor or your primary healthcare provider. They can help interpret the results in the context of your personal and family history, explain the implications for your reproductive health, and discuss the option of partner testing if necessary.
How common is this variant?
The rs121908745 variant is rare, with a global allele frequency of approximately 0.0003 in European non-Finnish populations according to gnomAD.
Frequently asked questions
What does it mean to be a carrier of a CFTR variant?
Being a carrier means you have one copy of a pathogenic variant in the CFTR gene. Carriers typically do not have symptoms of cystic fibrosis but can pass the variant to their children.
Is rs121908745 the same as DeltaF508?
No, they are different. DeltaF508 is the most common mutation causing cystic fibrosis, while rs121908745 (p.Arg553Ter) is a different, less common pathogenic variant.
Should I be worried if I am a carrier?
Being a carrier does not affect your own health. However, it is useful information for family planning, and you may want to discuss it with a genetic counselor.
Can I get tested for this variant?
Yes, this variant is included in many standard cystic fibrosis carrier screening panels. You can ask your doctor or a genetic counselor about ordering this test.
Sources & further reading
Educational information only, last refreshed 9/27/2026. 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.