CFTR rs76173977: Understanding the p.Trp1282Ter Variant
The rs76173977 variant in the CFTR gene, also known as p.Trp1282Ter (or W1282X), is a well-documented nonsense mutation. It is primarily recognized for its role as a pathogenic variant associated with cystic fibrosis, particularly within the Ashkenazi Jewish population.
What each genotype means
Typical CFTR gene profile
This genotype represents the most common sequence at this position in the CFTR gene. It does not include the W1282X nonsense mutation associated with cystic fibrosis carrier status.
This is the most common genotype found in all global populations.
Cystic fibrosis carrier status
This genotype indicates you carry one copy of the W1282X mutation, which is a well-established cause of cystic fibrosis when inherited in two copies. As a carrier, you typically do not have cystic fibrosis, but you may wish to discuss reproductive risk assessment with a genetic counselor or healthcare provider.
This genotype is most frequently observed in individuals of Ashkenazi Jewish ancestry, with an allele frequency of approximately 1.5% in that population.
Cystic fibrosis associated genotype
This genotype indicates the presence of two copies of the W1282X mutation. This mutation is a known cause of cystic fibrosis, a condition that affects the lungs and digestive system, and you should consult with a medical professional or clinical geneticist to discuss the clinical implications.
This genotype is extremely rare in the general population.
What is rs76173977?
The variant rs76173977, commonly referred to in clinical literature as p.Trp1282Ter or W1282X, is a specific genetic alteration located within the CFTR gene. In genetic terms, this is a nonsense mutation, meaning it introduces a premature stop codon in the DNA sequence. This change instructs the cell to stop building the CFTR protein before it is complete, typically resulting in a truncated, non-functional protein or the degradation of the messenger RNA through a process called nonsense-mediated decay. Because the protein cannot perform its intended role, this variant is classified as pathogenic, meaning it is known to cause disease when present in specific configurations.
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 gene is mutated, the resulting protein may be absent or dysfunctional, 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.
Research and Clinical Associations
Extensive research has established that the p.Trp1282Ter mutation is a significant cause of cystic fibrosis. It is frequently identified in clinical registries of individuals diagnosed with the condition. Because cystic fibrosis is an autosomal recessive disorder, an individual must typically inherit two copies of a pathogenic mutation—one from each parent—to manifest the disease. Carriers, who possess only one copy of this variant, generally do not exhibit symptoms of cystic fibrosis. However, the presence of this variant is clinically significant for family planning, as carriers are at risk of passing the mutation to their children. If both parents are carriers, there is a statistical probability of having a child affected by the condition.
Population Frequency
The frequency of the rs76173977 variant varies significantly across different ancestral groups. While it is relatively rare in the global population, with a gnomAD global allele frequency of approximately 0.0007, it is notably more common in individuals of Ashkenazi Jewish descent, where the allele frequency is approximately 0.015. This higher prevalence in specific populations has made it a standard target for carrier screening programs. Understanding these population-specific frequencies is essential for genetic counseling, as it helps clinicians determine the likelihood of an individual being a carrier based on their ancestry and family history.
What This Information Means for You
If you have been informed that you carry the rs76173977 variant, it is important to understand that this is a carrier status result. Being a carrier does not mean you have cystic fibrosis, nor does it mean you will develop the disease in the future. However, it does mean that you carry a genetic change that could be passed on to your biological children. If you are planning a family, you may wish to discuss this result with a genetic counselor or your healthcare provider. They can provide context regarding your specific situation, explain the risks for future children, and discuss options for partner testing. Always rely on professional medical guidance for interpreting genetic test results in the context of your personal health.
How common is this variant?
The rs76173977 variant has a global allele frequency of approximately 0.0007, but it is significantly more common in the Ashkenazi Jewish population, with an allele frequency of approximately 0.015.
Frequently asked questions
Is rs76173977 the same as W1282X?
Yes, rs76173977 and W1282X refer to the same genetic variant. W1282X is a protein-level description indicating that the tryptophan (W) at position 1282 has been replaced by a stop codon (X).
Does having this variant mean I have cystic fibrosis?
No, being a carrier of one copy of this variant does not mean you have cystic fibrosis. Cystic fibrosis is a recessive condition that typically requires two pathogenic mutations to manifest.
Should I be tested for cystic fibrosis if I am of Ashkenazi Jewish descent?
Carrier screening is often recommended for individuals of Ashkenazi Jewish descent due to the higher prevalence of certain CFTR mutations in this population. You should discuss the benefits and limitations of such testing with your doctor or a genetic counselor.
What should I do if my partner and I are both carriers?
If both partners are carriers of a CFTR mutation, there is a 25% chance with each pregnancy that the child will inherit two copies of the mutation and have cystic fibrosis. You should consult with a genetic counselor to discuss reproductive options and family planning.
Sources & further reading
Educational information only, last refreshed 10/15/2026. 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.