CFTR rs121908746: What Your Genotype Means
The rs121908746 variant, also known as p.Gly551Asp or G551D, is a specific genetic change in the CFTR gene. It is a well-documented pathogenic variant associated with cystic fibrosis, specifically affecting how the chloride channel protein functions within the cell.
What each genotype means
Typical CFTR function
This genotype represents the common, non-variant sequence at this position in the CFTR gene. Individuals with this genotype do not carry the specific G551D mutation associated with impaired chloride channel gating.
This is the most common genotype found in the general population across all ancestries.
Cystic fibrosis carrier status
This genotype indicates you carry one copy of the G551D mutation, which is associated with impaired chloride channel function. While typically asymptomatic, carriers may wish to discuss reproductive screening or family history with a genetic counselor, as cystic fibrosis is an autosomal recessive condition.
This genotype is rare, with the variant allele found at a global frequency of approximately 0.0006, and is most frequently observed in individuals of Northwestern European ancestry.
Potential cystic fibrosis diagnosis
This genotype indicates the presence of two copies of the G551D mutation, which is a known pathogenic variant that significantly impairs CFTR protein function. Individuals with this genotype should consult with a clinical geneticist or specialist, as this variant is associated with cystic fibrosis and may be eligible for specific CFTR modulator therapies like ivacaftor.
This genotype is extremely rare in the general population.
Understanding the Variant and the CFTR Gene
The rs121908746 variant is a missense mutation located in the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene. In this specific change, a guanine (G) is replaced by an adenine (A) at nucleotide position 1652, resulting in the substitution of the amino acid glycine with aspartic acid at position 551 of the protein. The CFTR gene provides instructions for creating a protein that acts as a channel, allowing negatively charged chloride ions to move in and out of cells. This movement is essential for maintaining the balance of salt and water on cell surfaces, which keeps mucus thin and free-flowing in organs like the lungs and pancreas. When this channel is defective, it can lead to the thick, sticky mucus characteristic of cystic fibrosis.
Clinical Significance and Research Associations
Research has established that the G551D variant is a 'gating mutation.' This means that while the CFTR protein is produced and successfully reaches the cell membrane, it fails to open properly in response to cellular signals, effectively blocking chloride transport. Because of this specific mechanism, the variant has been a major focus of precision medicine. It is a classic example of a mutation that responds to 'potentiator' therapies, such as ivacaftor, which are designed to help the channel stay open longer. Clinical studies have shown that patients with this mutation can experience significant improvements in lung function and sweat chloride levels when treated with these targeted modulators. The evidence for its role in cystic fibrosis is robust, and it is widely recognized in clinical genetics as a pathogenic variant.
Population Frequency
The G551D variant is relatively rare in the general population but is a significant contributor to cystic fibrosis cases in specific groups. Data from the Genome Aggregation Database (gnomAD) indicates that the allele frequency is very low, generally observed at less than 0.0006 globally. It is most frequently identified in individuals of Northwestern European descent. Because cystic fibrosis is a recessive condition, the presence of this variant in a single copy (carrier status) typically does not cause symptoms, but it is important for family planning and clinical screening. The distribution of this variant highlights the importance of ancestry-informed genetic testing, as its prevalence varies significantly across different global populations.
What You Can and Cannot Do With This Information
Genetic information regarding the CFTR gene is highly sensitive and should be interpreted within a clinical context. If you have received results indicating you carry this variant, it does not necessarily mean you have cystic fibrosis, as the condition typically requires inheriting two pathogenic variants (one from each parent). You cannot use this information to self-diagnose or make decisions about medical treatments. If you are concerned about your carrier status or family history, the most appropriate step is to consult with a certified genetic counselor or a medical professional. They can help you understand the implications of your results, discuss the necessity of further testing, and provide guidance on reproductive options. Always discuss any medication-related questions, especially regarding CFTR modulators, with your clinician or pharmacist.
How common is this variant?
The G551D variant is rare, with a global allele frequency of approximately 0.0006, and is primarily observed in populations of Northwestern European ancestry.
Frequently asked questions
What is the G551D mutation?
G551D is a specific genetic change in the CFTR gene that prevents the chloride channel from opening correctly. It is a well-known cause of cystic fibrosis and is classified as a gating mutation.
Is G551D the same as rs121908746?
Yes, rs121908746 is the unique identifier (rsID) used in scientific databases to refer to the G551D variant. Both terms describe the exact same genetic change.
Can G551D be treated with medication?
Yes, G551D is a target for CFTR modulator therapies like ivacaftor, which help the channel function more effectively. Please consult your doctor or pharmacist to discuss if such treatments are relevant to your specific clinical situation.
What does it mean to be a carrier of this variant?
Being a carrier means you have one copy of the variant and one normal copy of the gene. Carriers generally do not have cystic fibrosis symptoms but should speak with a genetic counselor regarding family planning.
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.