CFTR rs113993961: Understanding the F508del Variant
The rs113993961 variant in the CFTR gene, commonly known as F508del, is a three-base pair deletion that results in the loss of a single amino acid in the CFTR protein. This genetic change is the most frequent cause of cystic fibrosis, as it leads to the production of a misfolded protein that cannot properly reach the cell surface.
What each genotype means
Typical CFTR Function
You carry two non-deleted reference copies at this position. You do not carry the classic CFTR p.Phe508del (deltaF508) in-frame deletion variant. This finding indicates an average baseline population risk for CFTR-related disorders associated specifically with this site.
Found in approximately 96% to 98% of individuals of European ancestry and more than 99% of non-European populations.
Cystic Fibrosis Carrier
You carry one copy of the p.Phe508del (deltaF508) deletion and one intact reference copy. Cystic fibrosis is an autosomal recessive condition, meaning single-copy carriers typically do not develop classic multi-organ disease, though reproductive implications exist. A reproductive partner's CFTR carrier status determines whether future children might be at risk of inheriting two pathogenic variants.
Carried by approximately 1 in 25 to 1 in 30 individuals of European descent, but occurs much less frequently in East Asian and African ancestries.
What is the rs113993961 Variant?
The variant rs113993961, widely referred to in scientific literature as F508del or deltaF508, is a specific genetic alteration within the CFTR gene. It is characterized by the deletion of three nucleotides, which causes the removal of the amino acid phenylalanine at position 508 of the CFTR protein. This protein is a chloride channel that sits on the surface of epithelial cells, which line various organs including the lungs, pancreas, and digestive tract. Because this is an in-frame deletion, it does not shift the entire genetic code downstream, but it does fundamentally alter the structure of the resulting protein. This structural change is significant enough to prevent the protein from functioning correctly, making it a primary focus of research into the molecular mechanisms of genetic disease.
The Role of the CFTR Gene
The CFTR gene provides instructions for creating the cystic fibrosis transmembrane conductance regulator protein. This protein acts as a channel that transports negatively charged chloride ions into and out of cells. The movement of chloride ions helps control the movement of water in tissues, which is essential for the production of thin, freely flowing mucus. When the CFTR protein is absent or dysfunctional, the balance of salt and water is disrupted, leading to the production of thick, sticky mucus. This mucus can clog airways and ducts in the body, particularly in the lungs and pancreas. The F508del mutation is classified as a class II defect, meaning the protein is synthesized but fails to fold into its correct shape, causing the cell's quality control machinery to degrade it before it can reach the cell membrane.
Research and Clinical Associations
Extensive research has established that the F508del variant is the most common cause of cystic fibrosis worldwide. Clinical evidence from databases like ClinVar classifies this variant as pathogenic, meaning it is directly linked to the development of the disease. Studies have shown that the mutation disrupts the folding of the first nucleotide-binding domain (NBD1) of the protein and destabilizes the interface between different domains of the CFTR molecule. Because the protein cannot reach the cell surface, it cannot perform its role in chloride transport. While the evidence for its pathogenicity is strong, the severity of symptoms can vary between individuals due to other genetic and environmental factors. Current therapeutic research focuses on 'corrector' drugs, which are small molecules designed to help the misfolded protein achieve a shape that allows it to traffic to the cell surface.
Population Frequency
The F508del variant is particularly prevalent in populations of European ancestry. Carrier frequency is estimated to be approximately 1 in 25 to 1 in 30 individuals in these groups. Because cystic fibrosis is an autosomal recessive condition, an individual must typically inherit two copies of the pathogenic variant—one from each parent—to manifest the classic symptoms of the disease. Individuals who carry only one copy of the variant are generally asymptomatic carriers. The high frequency of this variant in certain populations is a subject of ongoing study in human genetics, as it suggests a potential historical evolutionary advantage for carriers, though the exact nature of this advantage remains a topic of scientific discussion.
Navigating Genetic Information
Understanding your genetic status regarding the CFTR gene can provide insights into your health and family planning. If you have received results indicating you carry the F508del variant, it is important to understand that this is a common finding in many populations. This information is not a medical diagnosis and does not predict the presence of disease on its own. If you are concerned about your health or your risk of passing this variant to children, you should consult with a genetic counselor or a healthcare provider. They can help interpret your results in the context of your personal and family medical history. Never make changes to your health management or medication based on genetic data without first discussing it with a qualified clinician or pharmacist.
How common is this variant?
The F508del variant is most common in European-ancestry populations, with a carrier frequency of approximately 1 in 25 to 1 in 30.
Frequently asked questions
What does it mean to be a carrier of F508del?
Being a carrier means you have one copy of the F508del mutation and one normal copy of the CFTR gene. Carriers typically do not show symptoms of cystic fibrosis but can pass the variant to their children.
Can F508del be treated?
Yes, there are medications known as CFTR modulators that help the misfolded protein function better. You should discuss these treatment options with a specialized clinician.
Is F508del the only cause of cystic fibrosis?
No, there are over 1,800 known mutations in the CFTR gene that can cause cystic fibrosis. F508del is simply the most common one identified.
How is F508del detected?
It is typically detected through genetic testing, such as a blood or saliva test, which looks for the specific three-base pair deletion in the CFTR gene.
Sources & further reading
Educational information only, last refreshed 10/11/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Severe pathogenic mutation (p.Gly542Ter) associated with cystic fibrosis.
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.
A pathogenic variant (p.Arg117His) in the CFTR gene associated with CFTR-related disorders.