rs113993960

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This is a inframe deletion variant in the CFTR gene.

Key Literature Trait Associations

Cystic Fibrosis

Homozygosity for F508del (rs113993960) causes classic cystic fibrosis with near-complete penetrance, characterized by pancreatic exocrine insufficiency (>90% of homozygotes), progressive obstructive lung disease, and elevated sweat chloride. F508del accounts for approximately 70% of CF alleles globally across 72,000+ CF chromosomes analyzed, making it the defining molecular lesion for CF diagnostics and newborn screening. Compound heterozygosity with other pathogenic CFTR alleles also produces CF. CFTR modulators targeting the F508del protein (e.g., elexacaftor/tezacaftor/ivacaftor) have substantially improved lung function and quality of life for homozygous patients.

Joseph L. Bobadilla et al. “Cystic fibrosis: A worldwide analysis ofCFTR mutations?correlation with incidence data and application to screening” Human Mutation (2002)
Allele DEL
OR —
p —
N 72,431
Preliminary work
multi-ancestry
Bélanger N et al. “Association between cystic fibrosis transmembrane regulator genotype and clinical outcomes, glucose homeostasis indices and CF-related diabetes risk in adults with CF.” Genetics and Molecular Biology (2024)
Allele DEL
OR —
p —
N 203
Candidate gene study
European

Congenital bilateral absence of the vas deferens

F508del is the most frequent CFTR allele identified in men with congenital bilateral absence of the vas deferens (CBAVD), a cause of obstructive azoospermia and male infertility. A systematic review and meta-analysis found F508del allele frequency of 17% in CBAVD patients overall, rising to 22% in Caucasian patients versus 8% in non-Caucasian individuals. Men compound heterozygous for F508del and the 5T intronic variant account for a substantial proportion of CBAVD cases. CFTR mutation screening (including F508del) is a standard component of the workup for male factor infertility due to obstructive azoospermia.

“CFTR mutations in men with congenital bilateral absence of the vas deferens (CBAVD): a systemic review and meta-analysis”
Allele DEL
OR —
p —
Meta-analysis
multi-ancestry
“Fertility treatment of azoospermic men with cystic fibrosis mutations: clinical and molecular findings”
Allele DEL
OR —
p —
N 639
Preliminary work
European

Chronic pancreatitis

Heterozygous or compound-heterozygous carriage of F508del is associated with a significantly elevated risk of chronic pancreatitis. A meta-analysis of 7 studies covering 64,832 patients found an overall OR of 3.20 (95% CI: 2.30–4.44) for F508del and chronic pancreatitis risk, with even stronger effects in Indian populations (OR 5.45). A broader 2025 meta-analysis of 138 studies encompassing 13,428 chronic pancreatitis patients found that 15.3% carried at least one pathogenic CFTR variant, underscoring CFTR as a major genetic contributor to pancreatitis susceptibility.

“Association between F508 deletion in CFTR and chronic pancreatitis risk”
Allele DEL
OR 3.20
p —
N 64,832
Preliminary work
multi-ancestry
Jiang J et al. “Prevalence of CFTR Pathogenic Variants in Pancreatitis: A Systematic Review and Meta-Analysis.” Clinical and Translational Gastroenterology (2025)
Allele DEL
OR —
p —
N 13,428
Preliminary work
multi-ancestry

Respiratory disease in CFTR carriers

Heterozygous F508del carriers in the general population show modestly elevated risk of respiratory conditions compared to non-carriers, despite a normal lifespan. In a population-based study of 108,034 Danish individuals, carriers had a 31% increased odds of chronic bronchitis (OR 1.31, 95% CI 1.16–1.48), an 88% increased hazard of bronchiectasis (HR 1.88, 95% CI 1.03–3.45), and a 52% increased hazard of lung cancer (HR 1.52, 95% CI 1.12–2.08). These findings suggest that even single-allele CFTR dysfunction has measurable but modest clinical consequences in airways.

Çolak Y et al. “Morbidity and mortality in carriers of the cystic fibrosis mutation CFTR Phe508del in the general population.” The European Respiratory Journal (2020)
Allele DEL
OR 1.31
p —
N 108,034
Preliminary work
European

Pancreatic cancer

CFTR mutations including F508del are associated with a modest but statistically significant increase in pancreatic cancer risk. A systematic review and meta-analysis of 5 case-control studies (1,674 pancreatic cancer cases, 19,036 controls) found that CFTR mutations overall increased pancreatic cancer risk (OR 1.41, 95% CI 1.07–1.84, P=0.013). The biological mechanism likely relates to chronic pancreatic inflammation from CFTR-mediated ductal dysfunction serving as a cancer precursor. Specific F508del data was not separately reported but this variant is the predominant CFTR allele in study populations.

Cazacu IM et al. “Pancreatitis-Associated Genes and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis.” Pancreas (2018)
Allele DEL
OR 1.41
p 1.3e-2
N 20,710
Meta-analysis
multi-ancestry

Gene information from NCBI Gene. Variant classifications from ClinVar.

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