CFTR rs121908756: Understanding the G551D Variant
The rs121908756 variant, commonly referred to as G551D, is a pathogenic mutation in the CFTR gene. It is primarily associated with cystic fibrosis and is a key marker included in many newborn and carrier screening panels.
What each genotype means
Typical CFTR function
This genotype represents the common, non-mutated sequence at this position in the CFTR gene. Individuals with this profile do not carry the specific G551D mutation associated with altered channel gating.
This is the most common genotype, found in the vast majority of the global population.
CFTR mutation carrier
This genotype indicates you carry one copy of the G551D mutation, also known as p.Gly551Asp. Research indicates this mutation impairs ATP-dependent channel gating in the CFTR protein, and carrying one copy typically does not cause cystic fibrosis symptoms but is relevant for reproductive carrier screening.
Carried by approximately 1 in 833 individuals of Northwest European descent, though frequencies vary significantly across different global populations.
Potential CFTR dysfunction
This genotype indicates you carry two copies of the G551D mutation. This mutation is known to abolish ATP-dependent gating of the CFTR channel, which is associated with cystic fibrosis; please consult with a medical geneticist or clinician to discuss the clinical implications of this result.
This genotype is extremely rare in the general population.
What is the rs121908756 Variant?
The variant rs121908756, frequently identified by the protein-level change p.Gly551Asp (or G551D), is a specific genetic alteration located within the CFTR gene. In genetic nomenclature, this variant is also documented as c.1652G>A. It represents a missense mutation, meaning a single nucleotide change results in the substitution of one amino acid for another in the final protein product. This specific change occurs in coding exon 12 of the gene. Because of its well-documented impact on protein function, it is classified as a pathogenic variant. It is widely recognized in clinical genetics and is included in many standard screening panels designed to identify individuals who may be carriers of cystic fibrosis-related mutations.
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 that transports negatively charged chloride ions into and out of cells. It also plays a critical role in regulating the movement of water and other ions across cell membranes, which is essential for maintaining the balance of salt and fluids in various tissues, including the lungs, pancreas, and digestive tract. When the CFTR gene contains pathogenic mutations, the resulting protein may be absent, non-functional, or unable to reach the cell surface properly. This disruption leads to the production of thick, sticky mucus, which is the hallmark of cystic fibrosis and can cause significant health challenges in the respiratory and digestive systems.
Research and Clinical Significance
Research has firmly established the G551D variant as a cause of classical cystic fibrosis. It is known to impair ATP-dependent channel gating, meaning the protein channel cannot open correctly to allow chloride transport. Because of this clear functional impact, the variant is highly prioritized in clinical diagnostic settings. It is also notable in the field of precision medicine; individuals with this specific mutation have been shown to respond to certain targeted therapies, such as ivacaftor, which are designed to improve the function of the CFTR protein. While the evidence for its pathogenicity is strong, clinical interpretation of any CFTR variant should always be conducted by a qualified healthcare professional or genetic counselor who can contextualize the findings within an individual's specific health history and family background.
Population Frequency
The frequency of the G551D variant varies across different ancestral groups. It is most commonly reported in populations of Northwest European descent, with an estimated frequency of approximately 0.0012. Because cystic fibrosis is an autosomal recessive condition, understanding the prevalence of such variants is vital for carrier screening programs. These programs aim to identify couples who are both carriers of pathogenic CFTR variants, as they may have an increased risk of having a child with cystic fibrosis. While screening panels have become more comprehensive, the distribution of specific mutations like G551D remains a focus of ongoing research to ensure that screening remains equitable and accurate across diverse global populations.
Navigating Genetic Information
If you have received information about your status regarding the rs121908756 variant, it is important to understand what this means in a clinical context. Being a carrier of a single pathogenic CFTR variant typically does not cause cystic fibrosis, as the condition is recessive and usually requires two pathogenic variants to manifest. However, this information is highly relevant for family planning and reproductive health. You cannot use this information to diagnose yourself or others, nor should it be used to make medical decisions without professional guidance. If you are concerned about your carrier status or the implications of this variant for your health or your family, please consult with a board-certified genetic counselor or your primary care physician. They can provide personalized interpretation and discuss the next steps for clinical testing or management.
How common is this variant?
The G551D variant has an estimated frequency of 0.0012 in populations of Northwest European descent. Its prevalence is monitored in clinical screening panels to assess carrier risk across diverse ancestries.
Frequently asked questions
What does it mean to be a carrier of the G551D variant?
Being a carrier means you have one copy of the G551D 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.
Is G551D the same as the DeltaF508 mutation?
No, G551D and DeltaF508 are different mutations in the CFTR gene. While both are associated with cystic fibrosis, they represent different genetic changes and may have different implications for treatment.
Can I be tested for this variant?
Yes, this variant is included in many standard cystic fibrosis carrier screening panels. You can discuss testing options with your doctor or a genetic counselor.
Does having this variant mean I have cystic fibrosis?
Cystic fibrosis is an autosomal recessive condition, meaning it usually requires two pathogenic mutations to cause the disease. A single variant does not typically result in a diagnosis of cystic fibrosis.
Are there treatments for people with the G551D mutation?
Yes, certain targeted therapies, such as ivacaftor, have been developed to treat cystic fibrosis in patients with specific mutations, including G551D. Please consult your clinician to discuss if any therapies are relevant to your specific medical situation.
Sources & further reading
Educational information only, last refreshed 10/15/2026. 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.