CFTR rs113993958: Understanding the p.Gly542Ter Variant
The rs113993958 variant in the CFTR gene, also known as p.Gly542Ter or G542X, is a well-characterized pathogenic mutation. It is strongly associated with cystic fibrosis, a condition caused by the loss of functional CFTR protein.
What each genotype means
Typical CFTR function
You have two functional copies of the CFTR gene at this position and do not carry the G542X mutation. This genotype is associated with normal chloride channel function and does not increase your risk of cystic fibrosis or carrier status for this specific allele. It does not rule out being a carrier of other variants in the CFTR gene.
Found in more than 99% of individuals across all major continental ancestral populations.
Cystic fibrosis carrier
You carry one normal CFTR allele and one copy of the c.1624G>T (p.Gly542Ter or G542X) nonsense mutation. Carriers are typically asymptomatic because one functional allele produces sufficient CFTR protein, though there is a reproductive risk of passing the variant to children. If your reproductive partner also carries a pathogenic CFTR variant, there is a 25% chance in each pregnancy of having a child affected by cystic fibrosis.
Carried by approximately 1 in 250 to 1 in 1,000 individuals of European descent, and observed less frequently in African, Asian, and Hispanic populations.
Cystic fibrosis affected
You have two copies of the c.1624G>T (p.Gly542Ter or G542X) nonsense mutation, which introduces a premature stop codon that severely impairs CFTR protein production. In medical literature, inheriting two severe CFTR loss-of-function variants is clinically diagnostic of cystic fibrosis, typically presenting with classical respiratory and pancreatic manifestations. Individuals with this genotype should consult a clinical geneticist or pulmonologist for comprehensive clinical evaluation and specialized care.
Extremely rare in the general population, occurring in fewer than 1 in 500,000 live births.
What is the rs113993958 Variant?
The rs113993958 variant, commonly referred to as p.Gly542Ter or G542X, is a specific genetic change located within the CFTR gene. In this variant, a single nucleotide substitution (a G-to-T change) introduces a premature termination codon at position 542 of the protein sequence. This type of mutation is known as a nonsense or stop-gained mutation. Because the genetic code is interrupted prematurely, the cellular machinery stops building the CFTR protein before it is complete. This typically results in a truncated, non-functional protein that the cell often degrades. Because the protein cannot perform its intended role, this variant is classified as a severe, pathogenic mutation. It is one of the most frequently studied variants in the context of cystic fibrosis research and is included in standard clinical screening panels for the condition.
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 particles called 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 protein is absent or dysfunctional, as occurs with the p.Gly542Ter mutation, chloride transport is impaired. This leads to the production of thick, sticky mucus that can clog airways and ducts in organs like the lungs and pancreas. Understanding this mechanism is central to developing therapies that aim to restore CFTR function or bypass the effects of premature stop codons.
Research and Clinical Significance
The p.Gly542Ter variant is widely recognized in medical literature as a pathogenic mutation. It is categorized as a Class I mutation, meaning it results in little to no functional protein production. Research consistently associates this variant with cystic fibrosis, particularly when it is present in combination with other CFTR mutations. Because it is a nonsense mutation, it has been a primary target for experimental therapies, such as readthrough agents designed to encourage the cell to ignore the premature stop signal and produce a full-length protein. While clinical trials for these therapies are ongoing, the evidence linking this specific variant to the disease phenotype is robust and well-established in clinical genetics. It is considered one of the most common disease-causing variants after p.Phe508del, making it a critical focus for both diagnostic testing and the development of mutation-specific treatments.
What You Can Do With This Information
If you have received information regarding your status for the rs113993958 variant, it is important to understand that this is a clinical finding that requires professional interpretation. This variant is associated with carrier status for cystic fibrosis, an autosomal recessive condition. Being a carrier generally does not cause symptoms, but it is relevant for family planning and reproductive health. If you are concerned about your genetic status or have a family history of cystic fibrosis, you should consult with a certified genetic counselor or a medical professional. They can help you understand the implications of your results, discuss the necessity of further testing, and provide context based on your personal and family health history. Never use genetic information to make independent medical decisions; always discuss your results and any potential health implications with your clinician.
How common is this variant?
The p.Gly542Ter variant is found at varying frequencies across different populations, with the highest prevalence observed in individuals of European descent. It is recognized as one of the most common pathogenic variants in cystic fibrosis patients globally.
Frequently asked questions
Is rs113993958 the same as G542X?
Yes, rs113993958 and G542X refer to the same genetic variant. G542X is the protein-level nomenclature, indicating that a glycine at position 542 is replaced by a stop codon.
What does it mean to be a carrier of this variant?
Being a carrier means you have one copy of the variant and one normal copy of the gene. Carriers typically do not show symptoms of cystic fibrosis but can pass the variant to their children.
Can this variant be treated?
Research into therapies for nonsense mutations like p.Gly542Ter is ongoing. While there is no cure, scientists are investigating drugs that may help the body produce functional protein despite the mutation.
Should I get tested for this variant?
Genetic testing for CFTR variants is often recommended for individuals with a family history of cystic fibrosis or those planning a family. You should discuss the appropriateness of this testing with your doctor or a genetic counselor.
Sources & further reading
Educational information only, last refreshed 10/27/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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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.
A pathogenic variant (p.Arg117His) in the CFTR gene associated with CFTR-related disorders.