CFTR rs113993963: Understanding the G542X Variant
The genetic variant rs113993963 represents a well-characterized nonsense change in the CFTR gene, historically denoted as G542X or p.Gly542Ter. This change introduces a premature stop codon during protein translation, disrupting normal CFTR channel production. Carrying one copy confers carrier status for autosomal recessive cystic fibrosis, while inheriting it alongside another pathogenic CFTR variant can lead to classic cystic fibrosis.
What each genotype means
Typical CFTR function
This genotype represents the common, functional sequence for this specific location in the CFTR gene. It does not carry the p.Gly542Ter nonsense mutation associated with cystic fibrosis.
This is the most common genotype, found in the vast majority of the global population.
Cystic fibrosis carrier status
This genotype indicates you carry one copy of the p.Gly542Ter mutation, also known as G542X. Carriers are typically healthy but may pass this variant to their children, which is a consideration for family planning if a partner also carries a CFTR mutation.
This genotype is rare, with a minor allele frequency of approximately 0.001 to 0.002 in European and Mediterranean populations.
Potential cystic fibrosis risk
This genotype indicates two copies of the p.Gly542Ter mutation. This specific change leads to premature termination of the CFTR protein, which is associated with severe classic cystic fibrosis. Individuals with this result should consult with a medical geneticist or specialist for clinical evaluation.
This genotype is extremely rare in the general population.
Variant Details and Genomic Context
The variant cataloged as rs113993963 is located within the CFTR gene on human chromosome 7. It is caused by a single nucleotide substitution, designated as c.1624G>T at the cDNA level, which leads to the protein alteration p.Gly542Ter (commonly known in legacy clinical literature as G542X). This change converts a codon that would typically encode a glycine residue into a premature stop codon (PTC). Consequently, cellular protein machinery terminates translation early, or the resulting mRNA transcript is degraded by cellular quality control pathways like nonsense-mediated decay. Because the variant truncates the protein before critical structural regions are synthesized, functional full-length CFTR channel production is severely compromised from this allele.
Biological Role of the CFTR Protein
The CFTR gene provides biological blueprints for the cystic fibrosis transmembrane conductance regulator protein. This protein functions as an epithelial ion channel that transports chloride and thiocyanate ions across cellular membranes throughout mucosal tissues, including the lungs, pancreas, gastrointestinal tract, and sweat glands. Proper ion transit allows water to follow passively by osmosis, maintaining a balanced, thin layer of fluid and lubricating mucus on organ surfaces. When CFTR function is severely decreased or missing entirely, secretions become excessively thick and sticky. This dehydration of epithelial linings impairs normal ciliated clearance in the airway and blocks pancreatic enzyme ducts, creating vulnerability to recurrent lung infections and digestive malabsorption.
Health Associations and Evidence
Cystic fibrosis is an autosomal recessive disorder, meaning an individual must inherit two dysfunctional CFTR alleles to develop the condition. Because rs113993963 produces a truncated, non-functional protein (Class I CFTR mutation), it is classified as a classic disease-causing variant in clinical databases such as ClinVar. Heterozygous carriers who have only one copy of rs113993963 and a fully functional second copy typically do not exhibit classic cystic fibrosis symptoms because one normal allele produces adequate ion channel activity. However, if an individual inherits rs113993963 alongside a second pathogenic CFTR variant—such as the common deltaF508 deletion—they are considered compound heterozygotes and are predisposed to classic, severe cystic fibrosis.
Population Frequency Across Ancestries
The rs113993963 variant is an uncommon allele globally, but it is one of the most frequently identified nonsense variants in CFTR among specific continental groups. In European-derived and Mediterranean populations, the minor allele frequency is typically observed between 0.001 and 0.002 (representing roughly 0.1% to 0.2% of alleles in those cohorts). The variant is observed at significantly lower frequencies or is entirely absent in large population samples of East Asian, South Asian, and African ancestries. Standard carrier screening panels in obstetric and preconception care frequently include this variant because of its established pathogenic status and relatively elevated prevalence among individuals of Mediterranean and European ancestry.
Interpreting Results and Clinical Perspective
Genetic data indicating the presence of rs113993963 provides informational insight into carrier status or disease predisposition, but it does not serve as a stand-alone medical diagnosis. Individuals who carry one copy may find the information useful for reproductive planning, particularly when considering partner screening. For individuals diagnosed with cystic fibrosis, knowing whether they carry a nonsense allele like G542X is clinically relevant, as certain CFTR modulator drugs work only on specific mutation classes; research is ongoing regarding targeted therapies for premature stop codons. Anyone interpreting genetic findings should consult a certified genetic counselor, pulmonologist, or medical geneticist to ensure comprehensive diagnostic confirmation and clinical guidance.
How common is this variant?
The rs113993963 variant has a minor allele frequency of approximately 0.001 to 0.002 in European and Mediterranean ancestries, and is exceedingly rare or absent in East Asian and African populations.
Frequently asked questions
What is the CFTR G542X mutation?
G542X (or p.Gly542Ter) is a legacy clinical designation for rs113993963. It is a nonsense mutation in the CFTR gene that stops protein production prematurely, preventing the cell from creating a working chloride channel from that allele.
Does carrying one copy of rs113993963 mean I have cystic fibrosis?
No, carrying a single copy simply makes you an unaffected carrier because cystic fibrosis is an autosomal recessive condition. A person must have two disrupted CFTR alleles—one from each parent—to show classic clinical disease.
Why is rs113993963 included in carrier screening tests?
While thousands of variants have been observed across the CFTR gene, rs113993963 is one of the most common nonsense mutations, particularly in people of Mediterranean and European descent. Detecting it allows prospective parents to assess reproductive risks.
Can standard CFTR modulator medications treat the G542X variant?
Many currently approved CFTR modulators require at least some full-length protein at the cell surface to work, which pure nonsense mutations do not provide. Patients should speak with their pulmonologist or CF care team regarding clinical trials and treatments appropriate for their specific mutation profile.
Sources & further reading
Educational information only, last refreshed 9/6/2026. 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.