CFTR rs80034449: Understanding the p.Arg334Trp Variant
The rs80034449 variant in the CFTR gene, also known as p.Arg334Trp, is a genetic change where a single nucleotide substitution alters the CFTR protein. This variant is recognized as pathogenic and is associated with cystic fibrosis, a condition affecting the body's chloride-channel function.
What each genotype means
Typical CFTR genotype
This genotype represents the common, non-variant sequence at this position in the CFTR gene. It is not associated with the pathogenic p.Arg334Trp mutation linked to 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 pathogenic p.Arg334Trp variant, also known as c.1000C>T. This variant is classified as pathogenic and is associated with cystic fibrosis or atypical CF-related conditions; you should consult with a genetic counselor or clinician to discuss what this means for your health and family planning.
This genotype is rare, with the variant allele occurring at a global frequency of approximately 0.00008, though it is more frequently observed in certain European populations.
Pathogenic CFTR variant
This genotype indicates you carry two copies of the p.Arg334Trp variant. This is a pathogenic mutation associated with classic or atypical cystic fibrosis, and you should discuss these results with a medical professional or specialist to understand the clinical implications for your health.
This genotype is extremely rare in the general population.
What is the rs80034449 Variant?
The rs80034449 variant is a single nucleotide polymorphism (SNP) located within the CFTR gene on chromosome 7. Specifically, it involves a change at the DNA level where a cytosine is replaced by a thymine, resulting in the substitution of the amino acid arginine with tryptophan at position 334 of the CFTR protein. This specific change is often referred to in clinical literature as p.Arg334Trp or R334W. Because this alteration occurs in the coding region of the gene, it can impact the structure and function of the resulting protein. Genetic variants like this are identified through clinical sequencing and are cataloged in databases to help researchers and clinicians understand their potential impact on human health. It is categorized as a missense variant, meaning the change results in a different amino acid being incorporated into the protein chain during synthesis.
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 gene contains pathogenic variants, the resulting protein may be absent, non-functional, or present in reduced amounts. This disruption leads to the production of thick, sticky mucus that can clog airways and ducts in various organs, particularly the lungs and pancreas. Understanding the function of this gene is essential for grasping why specific variants, such as rs80034449, are studied in the context of cystic fibrosis and related conditions.
Clinical Associations and Evidence
Research has classified the p.Arg334Trp variant as pathogenic, meaning it is known to contribute to the development of cystic fibrosis. Clinical studies have observed that individuals carrying this variant may exhibit symptoms consistent with classic or atypical cystic fibrosis. Interestingly, some research has noted that patients with this specific mutation might show variations in disease progression, such as a later age of onset for certain respiratory complications like Pseudomonas aeruginosa colonization, compared to other CFTR mutations. However, the clinical presentation can be highly variable, and the presence of this variant does not guarantee a specific severity of disease. Because cystic fibrosis is a complex, multi-system condition, the impact of any single variant is often influenced by other genetic factors and environmental modifiers. Clinical interpretation of this variant is supported by functional studies demonstrating that the R334W change impairs the normal traffic and activity of the CFTR protein.
Population Frequency
The rs80034449 variant is considered rare in the general population. According to data from the Genome Aggregation Database (gnomAD), the global allele frequency is approximately 0.00008. While it is found across various ancestral groups, it is observed at a slightly higher frequency in populations of European descent. Because it is a rare variant, most individuals do not carry it. Genetic screening panels often include this variant because of its established link to cystic fibrosis, particularly in populations where the condition is more prevalent. It is important to note that carrier frequency for CFTR variants can vary significantly between different ethnic and geographic groups. Understanding these frequency patterns helps public health experts and genetic counselors provide context during carrier screening, though individual results should always be interpreted by a qualified healthcare professional in the context of a person's full clinical and family history.
What This Information Means for You
If you have received information about the rs80034449 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 typically means an individual has one copy of a pathogenic variant and one normal copy of the gene, which usually does not result in the disease itself. However, if both parents are carriers of pathogenic CFTR variants, there is a risk of passing the condition to their children. This information should not be used for self-diagnosis or to make medical decisions. If you are concerned about your carrier status or family history, you should consult with a genetic counselor or a physician. They can provide appropriate testing, explain the implications of your results, and discuss reproductive options or clinical management if necessary.
How common is this variant?
The rs80034449 variant is rare, with a global allele frequency of approximately 0.00008, though it is more frequently observed in European populations.
Frequently asked questions
Is rs80034449 the same as cystic fibrosis?
No, rs80034449 is a specific genetic variant within the CFTR gene. While it is associated with cystic fibrosis, having the variant does not automatically mean you have the disease, especially if you are a carrier.
What should I do if I am a carrier of this variant?
If you are identified as a carrier, it is recommended to speak with a genetic counselor. They can help you understand what this means for your health and your family planning.
Can this variant be treated?
Cystic fibrosis is managed through various medical therapies that target the symptoms and the underlying protein dysfunction. You should discuss any medical concerns or potential treatments with a specialist, such as a pulmonologist.
Why is this variant included in carrier screening?
It is included because it is a known pathogenic variant that can contribute to cystic fibrosis. Screening helps identify individuals who may be carriers so they can make informed reproductive health decisions.
Sources & further reading
Educational information only, last refreshed 10/14/2026. 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.