CFTR rs113993965: Understanding the G542X Variant
The rs113993965 variant in the CFTR gene, commonly referred to as G542X or p.Gly542Ter, is a well-documented pathogenic nonsense mutation. It is primarily associated with cystic fibrosis when inherited in combination with another pathogenic CFTR variant.
What each genotype means
Typical CFTR function
You carry two reference copies of this CFTR site and do not carry the G542X pathogenic nonsense variant. This result does not indicate carrier status for this specific mutation, though it does not rule out other possible CFTR variants elsewhere in the gene. Overall risk for cystic fibrosis related to this particular locus remains at the baseline population level.
Found in greater than 99.8% of individuals globally across most major continental populations.
Cystic fibrosis carrier
You carry one copy of the pathogenic nonsense variant known in medical literature as G542X (or c.1624G>T), which classifies you as an asymptomatic cystic fibrosis carrier. Carriers typically do not experience symptoms because the single functional CFTR copy produces sufficient protein, but they have a 50% chance of passing this variant to their biological children. If planning a pregnancy, discussing reproductive carrier screening with a genetic counselor or healthcare provider is commonly recommended.
Carried by approximately 1 in 500 to 1 in 1,000 individuals of European and Mediterranean descent; substantially less frequent in East Asian populations.
Classic cystic fibrosis genotype
This genotype indicates two copies of the severe G542X premature stop codon mutation, which halts normal production of functional CFTR ion channels. In clinical research, homozygous nonsense mutations are strongly associated with classic cystic fibrosis typically characterized by pancreatic insufficiency and progressive respiratory symptoms. Individuals with this genotype should review their clinical profile and therapeutic options with a cystic fibrosis specialist or medical geneticist.
Extremely rare globally, occurring in fewer than 1 in 1,000,000 individuals in the general population.
What is the rs113993965 Variant?
The rs113993965 variant is a specific change in the DNA sequence of the CFTR gene. In scientific literature, it is frequently identified as G542X, which indicates that a glycine amino acid at position 542 of the CFTR protein is replaced by a premature stop codon. This type of change is known as a nonsense mutation. Because the stop signal occurs earlier than it should, the cell often triggers a process called nonsense-mediated decay, which degrades the messenger RNA before it can be used to build a functional protein. Consequently, this variant typically results in a complete loss of functional CFTR protein production from the affected allele. It is recognized as one of the most common pathogenic variants in the CFTR gene and is included in standard clinical screening panels for cystic fibrosis carriers.
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 that transports negatively charged chloride ions into and out of cells. This movement of ions is essential for maintaining the proper balance of salt and water on cell surfaces, which helps produce thin, free-flowing mucus in organs like the lungs, pancreas, and digestive tract. When the CFTR protein is absent or dysfunctional, the mucus becomes thick and sticky, leading to the characteristic symptoms of cystic fibrosis. Because the G542X variant prevents the production of a functional channel, it is classified as a Class I mutation, meaning it causes a severe defect in protein synthesis. Understanding this mechanism is critical for researchers developing therapies aimed at bypassing premature stop signals to restore protein function.
Research and Clinical Significance
Research into rs113993965 has established it as a pathogenic variant, meaning it is known to cause disease when present in specific genetic configurations. Cystic fibrosis is an autosomal recessive condition, which means an individual must inherit two pathogenic variants—one from each parent—to manifest the disease. If an individual carries only one copy of G542X, they are considered a carrier and typically do not show symptoms of cystic fibrosis. However, if they inherit G542X alongside another pathogenic CFTR variant, they may develop the condition. Clinical studies have shown that the severity of the disease can vary depending on the second mutation present. While some research explores experimental therapies like read-through agents to help the cell ignore the premature stop signal, these treatments are currently largely in the research or clinical trial phases.
Population Frequency
The G542X variant is not evenly distributed across all global populations. Data from the Genome Aggregation Database (gnomAD) indicates that the variant is relatively rare in the general population, with an overall allele frequency of approximately 0.0007. However, it is more prevalent in specific ancestral groups, particularly among individuals of European and Mediterranean descent, where the frequency can reach approximately 0.1%. Because cystic fibrosis is more common in these populations, carrier screening for this specific variant is a standard practice in many clinical settings. It is important to note that population frequencies are estimates based on large databases and may not reflect the risk for every individual. Genetic testing results should always be interpreted by a qualified healthcare professional who can provide context based on personal and family medical history.
What You Can Do With This Information
If you have received information about your status regarding the rs113993965 variant, the most important step is to discuss the results with a genetic counselor or your primary care physician. This information is primarily used for carrier screening and family planning. If you are a carrier, it does not mean you have cystic fibrosis, but it does mean there is a possibility of passing the variant to your children. If you are considering family planning, a genetic counselor can help you understand the risks and the implications of your partner's genetic status. Please remember that this information is for educational purposes and should not be used to diagnose or treat any medical condition. Never make changes to your health management or medication regimen based on genetic data without consulting a qualified clinician or pharmacist.
How common is this variant?
The G542X variant has a global allele frequency of approximately 0.0007, with higher prevalence in European and Mediterranean populations at about 0.1%.
Frequently asked questions
Is G542X the same as cystic fibrosis?
No, G542X is a specific genetic variant that can cause cystic fibrosis. You must inherit two pathogenic CFTR variants to have the disease; carrying only one copy of G542X makes you a carrier but typically does not cause symptoms.
Should I get tested for the G542X variant?
Genetic testing for CFTR variants is often recommended for individuals with a family history of cystic fibrosis or those planning a pregnancy. You should discuss the necessity and implications of this testing with your doctor or a genetic counselor.
Can G542X be treated with current medications?
While some CFTR modulators are used for cystic fibrosis, they are often designed for specific mutations. G542X is a nonsense mutation, which presents unique challenges for current therapies, and research into new treatments is ongoing.
What does it mean if I am a carrier of G542X?
Being a carrier means you have one copy of the variant and one normal copy of the gene. It does not affect your health, but it means there is a chance you could pass the variant to your children.
Sources & further reading
Educational information only, last refreshed 10/28/2026. 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.
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.