CFTR rs77931234: What Your Genotype Means
The genetic variant rs77931234 is a rare single nucleotide polymorphism located in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. It introduces a premature stop codon that results in a truncated, nonfunctional CFTR protein. When inherited alongside another pathogenic variant on the second chromosome copy, it is associated with cystic fibrosis, while carrying a single copy typically reflects carrier status.
What each genotype means
Typical CFTR genotype
This genotype represents the absence of the specific variant rs77931234. Individuals with this profile do not carry this specific premature termination codon variant in the CFTR gene.
This is the most common genotype, found in the vast majority of the global population.
CFTR variant carrier
You carry one copy of the rs77931234 variant, which is associated with a premature termination codon in the CFTR gene. Being a carrier of a single pathogenic CFTR variant does not typically cause cystic fibrosis, but you should discuss your carrier status and potential implications for family planning with a genetic counselor or clinician.
This genotype is rare, occurring in approximately 1 in 25,000 individuals based on a reported allele frequency of 0.00002 in European populations.
Potential CFTR variant homozygote
You carry two copies of the rs77931234 variant. Because this variant is linked to a premature termination codon, inheriting two copies may significantly impact CFTR protein function and is associated with the risk of developing cystic fibrosis. Please consult with a medical geneticist or specialist to discuss these findings in the context of your clinical health.
This genotype is extremely rare, occurring in approximately 1 in 2.5 billion individuals based on the reported allele frequency.
What is rs77931234 and Where is It Found?
The variant rs77931234 represents a specific point mutation within the CFTR gene on human chromosome 7. The CFTR gene contains the biological instructions for building an epithelial ion channel that regulates salt and fluid transport across cell membranes. At rs77931234, a single base substitution alters the normal codon sequence, converting an amino acid codon into a premature stop signal, also termed a nonsense mutation. In molecular genetics, this type of change halts protein translation before the full polypeptide chain can be synthesized. Cells frequently target such altered messenger RNA transcripts for degradation through a cellular quality-control pathway known as nonsense-mediated decay. Consequently, very little to no functional CFTR protein is generated from an allele carrying this alteration.
The Biological Role of the CFTR Gene
The CFTR protein functions as an ATP-binding cassette transporter channel primarily located on the apical membrane of epithelial cells. These cells line key organs such as the lungs, pancreas, gastrointestinal tract, and sweat glands. Proper passage of chloride and bicarbonate ions across these tissues ensures the hydration of mucosal surfaces. When CFTR function is severely reduced or completely missing, secretions become excessively thick and sticky. In the respiratory system, this thick mucus impairs normal airway clearance, creating an environment susceptible to recurring bacterial infections and chronic inflammation. In the digestive system, blocked pancreatic ducts prevent essential digestive enzymes from reaching the intestines, leading to exocrine pancreatic insufficiency and malabsorption.
Clinical Evidence and Associated Conditions
Cystic fibrosis is an autosomal recessive disorder, which means that clinical symptoms typically manifest only when an individual inherits two pathogenic CFTR variants—one on each homologous chromosome. Clinical databases including ClinVar classify rs77931234 as a pathogenic variant because nonsense variants predictably disrupt protein synthesis. Heterozygous carriers who possess one typical allele and one rs77931234 variant allele generally do not show classic signs of cystic fibrosis because a single functional copy provides sufficient channel activity for systemic health. However, in rare instances, CFTR carriers have shown statistical associations with milder CFTR-related disorders, such as chronic rhinosinusitis, recurrent idiopathic pancreatitis, or isolated bronchiectasis.
Population Frequency and Demographics
According to population genomics data from the Genome Aggregation Database (gnomAD), rs77931234 is an exceptionally rare variant. Its observed allele frequency is approximately 0.00002 in European populations, representing roughly two copies per one hundred thousand chromosomes analyzed. Across other global ancestries, including African, East Asian, and South Asian populations, the variant is observed either at similarly low frequencies or not detected at all in standard reference cohorts. Because the allele is so scarce, homozygous individuals (possessing two copies of rs77931234) are exceedingly rare in the general public. Instead, clinical occurrences of disease involving this variant almost exclusively involve compound heterozygosity with more common CFTR alleles such as F508del.
Interpreting Results and Limitations of Genetic Data
Identifying an rs77931234 variant on a commercial direct-to-consumer panel or clinical screening test requires cautious interpretation. Because raw genotyping arrays occasionally produce false-positive calls for extremely rare variants, unconfirmed results should be verified via targeted clinical Sanger sequencing or next-generation sequencing. Genetic data provide probabilities and carrier status rather than definitive health outcomes. Finding this variant does not indicate personal disease in an asymptomatic individual with one mutated allele, though it carries implications for reproductive planning. Anyone with questions regarding carrier status, family planning, or symptoms should consult a certified genetic counselor or qualified medical provider to interpret results within their full clinical and family context.
How common is this variant?
The rs77931234 variant is exceedingly rare worldwide, with an estimated allele frequency of approximately 0.00002 (around 1 in 50,000 alleles) in European populations according to gnomAD datasets, and it is rarely observed in other global ancestries.
Frequently asked questions
Does having the rs77931234 variant mean I have cystic fibrosis?
No. Having a single copy of rs77931234 means you are an unaffected genetic carrier. Cystic fibrosis is an autosomal recessive condition that generally occurs only when a person inherits two disease-causing variants, one from each parent.
Can CFTR modulator medications treat the rs77931234 variant?
Because rs77931234 creates a premature stop codon (nonsense variant), the cell typically breaks down the message and produces little or no functional protein. Current approved small-molecule modulators mainly target misfolded or defective channels, so nonsense variants often require different investigational approaches. Patients should consult their care team regarding variant-specific therapies.
What does this variant mean for having children?
If you are a carrier of rs77931234, there is a 50% chance you will pass this allele to any child you have. However, a child would only be at risk of developing cystic fibrosis if your reproductive partner also carries a pathogenic CFTR variant. Reproductive carrier screening and genetic counseling can provide personalized risk estimates.
Should I confirm this finding with a medical-grade test?
Yes. If this result came from a direct-to-consumer test or consumer microarray, clinical confirmation using an accredited laboratory is strongly recommended. Microarrays have higher false-positive rates for extremely rare variants, so clinical-grade sequencing is needed before making medical or reproductive decisions.
Sources & further reading
Educational information only, last refreshed 9/8/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This variant (p.Gly542Ter) is a severe pathogenic mutation in the CFTR gene, commonly screened for cystic fibrosis carrier status.
Classic cystic fibrosis in-frame 3-bp deletion variant (p.Phe508del / deltaF508) causing misfolding and impaired chloride channel trafficking.
Frameshift mutation c.3659delC (p.Thr1220Lysfs) 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.
This variant is associated with cystic fibrosis carrier status and modulates the efficacy of ivacaftor treatment.