CFTR rs121908758: Understanding the p.Trp1282Ter Variant
The rs121908758 variant in the CFTR gene is a well-documented pathogenic stop-gain mutation, also known as p.Trp1282Ter. It is primarily associated with autosomal recessive cystic fibrosis and is a key marker used in carrier screening programs.
What each genotype means
Typical CFTR genotype
This genotype represents the common, non-pathogenic sequence at this position in the CFTR gene. It does not carry the W1282X mutation associated with cystic fibrosis.
This is the most common genotype found in the general population across all ancestries.
Cystic fibrosis carrier
This genotype indicates you carry one copy of the W1282X mutation, which results in a truncated, non-functional CFTR protein. As an autosomal recessive condition, carrying one copy typically does not cause cystic fibrosis symptoms, but it is important for reproductive risk assessment; consult a genetic counselor to discuss implications.
This genotype is found in approximately 0.0016 of the Ashkenazi Jewish population and is rarer in other global populations.
Cystic fibrosis affected
This genotype indicates two copies of the W1282X mutation, which is a known pathogenic variant that prevents the production of functional CFTR protein. This is associated with the development of cystic fibrosis, a condition requiring specialized medical management; please discuss these results with a healthcare provider or clinical geneticist.
This genotype is extremely rare in the general population.
What is the rs121908758 Variant?
The rs121908758 variant, commonly referred to as p.Trp1282Ter or W1282X, is a specific change in the DNA sequence of the CFTR gene. In this variant, a single nucleotide substitution leads to a premature stop codon in the protein-coding sequence. This type of mutation is known as a 'stop-gain' or 'nonsense' mutation. Instead of the cellular machinery reading the full instructions to build a complete protein, the process is cut short at this specific location. This results in a truncated, non-functional protein or the degradation of the messenger RNA (mRNA) through a process called nonsense-mediated decay. Because the CFTR protein is essential for normal cellular function, the loss of this protein's activity is a significant event at the molecular level.
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. It is responsible for transporting 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 protein is absent or dysfunctional, the mucus becomes thick and sticky, which can clog airways and ducts in the lungs, pancreas, and other organs. This disruption is the underlying cause of the symptoms associated with cystic fibrosis.
Clinical Associations and Evidence
The rs121908758 variant is classified as pathogenic, meaning it is strongly linked to the development of cystic fibrosis when inherited in a specific pattern. Because cystic fibrosis is an autosomal recessive condition, an individual typically needs to inherit two copies of a pathogenic variant—one from each parent—to manifest the disease. If an individual carries only one copy, they are considered a carrier and generally do not show symptoms of the condition. Clinical evidence for this variant is robust, with multiple submissions to databases like ClinVar confirming its role in classic cystic fibrosis, including symptoms like pancreatic insufficiency. Research is ongoing into therapeutic strategies, such as translational readthrough-inducing drugs, which aim to help the cell bypass the premature stop codon and produce a functional protein.
Population Frequency
The frequency of the rs121908758 variant varies significantly across different ancestral groups. It is most notably observed in individuals of Ashkenazi Jewish descent, where the carrier frequency is approximately 0.0016. In the broader global population, as represented in the gnomAD database, the frequency is much lower, estimated at approximately 0.0002. These differences highlight the importance of ancestry-informed genetic screening. Because the variant is more common in specific populations, it is frequently included in targeted carrier screening panels for those groups to help individuals understand their reproductive risks. Understanding these frequencies is a critical component of genetic counseling and public health initiatives aimed at managing hereditary conditions.
What This Information Means for You
If you have received information about your status regarding the rs121908758 variant, it is important to understand that this is a clinical finding that requires professional interpretation. Being a carrier of this variant does not mean you have cystic fibrosis, but it does mean you have a higher chance of passing the variant to your children. If both parents are carriers of a pathogenic CFTR variant, there is a 25% chance with each pregnancy that the child will inherit two copies and potentially develop cystic fibrosis. This information is intended for educational purposes and should not be used for self-diagnosis. If you have concerns about your carrier status or family history, you should consult with a certified genetic counselor or a medical professional who can provide personalized guidance based on your specific genetic results and clinical context.
How common is this variant?
The variant has a frequency of 0.0016 in Ashkenazi Jewish populations and approximately 0.0002 in the general population according to gnomAD data.
Frequently asked questions
What is the rs121908758 variant?
The rs121908758 variant is a specific genetic change in the CFTR gene, also known as p.Trp1282Ter. It is a pathogenic mutation that causes a premature stop in the production of the CFTR protein.
Does having this variant mean I have cystic fibrosis?
Not necessarily. Cystic fibrosis is an autosomal recessive condition, meaning you typically need two copies of a pathogenic variant to have the disease. If you have only one copy, you are a carrier and generally do not have the disease.
Should I be tested for this variant?
Carrier screening is often recommended for individuals with a family history of cystic fibrosis or those from populations where the variant is more common. You should discuss the appropriateness of genetic testing with your healthcare provider or a genetic counselor.
Can this variant be treated?
While there is no cure for the underlying genetic cause, research into therapies like translational readthrough-inducing drugs is ongoing. Current treatments for cystic fibrosis focus on managing symptoms and improving quality of life.
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.