CFTR rs113993962: Understanding Cystic Fibrosis Carrier Status
The rs113993962 variant is a well-characterized single-nucleotide change in the CFTR gene, historically known as G542X or c.1624G>T. It introduces a premature stop codon that results in a truncated, non-functional ion channel protein. Carrying one copy of this variant confers carrier status for autosomal recessive cystic fibrosis, meaning carriers typically remain asymptomatic while having reproductive implications.
What each genotype means
Typical CFTR gene profile
This genotype represents the common, non-variant sequence at this position in the CFTR gene. It does not carry the specific G542X (c.1624G>T) mutation associated with cystic fibrosis carrier status.
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 G542X (c.1624G>T) pathogenic variant. This variant is a known cause of cystic fibrosis when inherited in two copies, and individuals with one copy are considered carriers who do not typically exhibit symptoms of the disease themselves. You should discuss this result with a genetic counselor or healthcare provider to understand implications for family planning.
This genotype is found in approximately 1 in 500 to 1 in 1,000 individuals in many European and Mediterranean populations, though frequencies vary significantly by ancestry.
Cystic fibrosis associated genotype
This genotype indicates you carry two copies of the G542X (c.1624G>T) pathogenic variant. This variant is a nonsense mutation that leads to a premature stop codon, typically resulting in the production of non-functional CFTR protein. Individuals with this genotype are at high risk for cystic fibrosis and should consult with a medical specialist for clinical evaluation and management.
This genotype is extremely rare in the general population, occurring primarily in individuals affected by cystic fibrosis.
Genetic Architecture and Molecular Impact
The single-nucleotide variant rs113993962 represents a guanine-to-thymine substitution (c.1624G>T) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7. At the protein level, this alteration converts a codon for glycine at position 542 into a premature stop codon, designated as p.Gly542Ter or G542X. Because it is a nonsense mutation, it falls into Class I of CFTR variants, characterized by defective protein synthesis. Cells reading this mRNA typically trigger nonsense-mediated mRNA decay or yield severely shortened, non-functional polypeptides. Consequently, the variant produces no viable channel protein at the apical epithelial membrane. Unlike missense alterations where a defective channel reaches the cell surface or matures poorly, Class I nonsense alleles completely disrupt normal channel production from the affected allele.
Biological Function of the CFTR Channel
The CFTR gene encodes an ATP-binding cassette transporter that functions as an epithelial chloride and bicarbonate channel. Found throughout the airways, digestive tract, pancreas, sweat glands, and reproductive organs, CFTR regulates electrolyte balance and fluid movement across epithelial tissues. Functional channels facilitate fluid secretion, which keeps mucus thin and hydrated in the respiratory and gastrointestinal tracts. When CFTR function is severely compromised, epithelial secretions become thick and dehydrated, leading to mucociliary clearance failure, recurrent pulmonary infections, and pancreatic insufficiency. Because CFTR is inherited in an autosomal recessive manner, possessing a single functional copy of the gene is sufficient to sustain adequate epithelial fluid transport in heterozygous individuals.
Clinical Evidence and Carrier Status
According to the ClinGen Gene-Disease Validity database, CFTR is definitively associated with autosomal recessive cystic fibrosis. The rs113993962 variant is classified as pathogenic across major clinical databases, including ClinVar. When an individual inherits rs113993962 alongside another severe CFTR pathogenic variant in trans (compound heterozygosity) or inherits two copies, classic cystic fibrosis manifests. However, individuals with one mutated copy and one normal allele are healthy carriers. Standard clinical panels recommended by the American College of Medical Genetics and Genomics (ACMG) routinely include rs113993962 because it is one of the most common nonsense mutations worldwide, second only to the common F508del deletion in many global studies.
Interpreting Results and Reproductive Considerations
Identifying an rs113993962 variant on a carrier screen or direct-to-consumer genetic test provides information regarding carrier status and reproductive risk, not an active medical diagnosis for the carrier. Carriers do not typically experience classic cystic fibrosis symptoms because their unaffected allele provides adequate CFTR channel function. The primary utility of this genetic information centers on family planning. If both reproductive partners are confirmed carriers of a CFTR disease-causing variant, each pregnancy carries a 25% statistical risk of inheriting two altered copies and developing cystic fibrosis. Genetic counseling is standard practice to review residual risks, partner carrier testing, and reproductive options, as commercial assays vary in the specific CFTR variants they evaluate.
How common is this variant?
The rs113993962 variant has an allele frequency of approximately 0.001 (0.1%) in non-Finnish European populations and reaches higher frequencies of around 0.002 to 0.06 in Mediterranean populations, where it represents one of the most prevalent CFTR mutations.
Frequently asked questions
Does having the rs113993962 variant mean I have cystic fibrosis?
No, having a single copy (GT genotype) means you are an unaffected carrier. Cystic fibrosis is an autosomal recessive condition that requires inheriting two disease-causing CFTR mutations, one from each parent.
What is the G542X mutation in CFTR?
G542X is the historical protein notation for the variant rs113993962 (c.1624G>T, p.Gly542Ter). It is a nonsense mutation that introduces an early stop signal, preventing the production of functional CFTR protein from that copy.
Why is rs113993962 included in standard carrier screening panels?
The variant is one of the most common pathogenic CFTR mutations identified in populations worldwide, particularly among individuals of Mediterranean descent. Medical professional guidelines recommend screening for it to help individuals and couples understand their reproductive risks.
If I am a carrier of rs113993962, will my children have cystic fibrosis?
Your children will only be at risk of developing cystic fibrosis if your reproductive partner is also a carrier of a pathogenic CFTR mutation. If both parents are carriers, there is a 25% chance with each pregnancy that the child will inherit both mutations and have cystic fibrosis.
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.