Is CFTR p.Arg792Ter (c.2374C>T) pathogenic?

CFTR p.Arg792Ter (c.2374C>T) is classified Pathogenic in CFTR (ClinVar, Expert panel, 10 submitters; last evaluated 2017-03-17). Very rare (popmax 0.00418%, afr); Associated with cystic fibrosis.

How common is CFTR p.Arg792Ter (c.2374C>T) in the general population?

CFTR p.Arg792Ter (c.2374C>T) is very rare (popmax 0.00418%, afr) (gnomAD).

How is Cystic fibrosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CFTR p.Arg792Ter

Q: What condition is associated with CFTR p.Arg792Ter (c.2374C>T)?

CFTR p.Arg792Ter (c.2374C>T) is associated with cystic fibrosis, bronchiectasis with or without elevated sweat chloride 1, congenital bilateral aplasia of vas deferens from CFTR mutation (ClinVar).

c.2374C>T · rs145449046 · VCV53483

Pathogenic Expert panel

Classification

Pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 10 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00418%, afr)

Conditions

cystic fibrosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 14 of 27
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.37	GERP -0.41
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00418% African / African-American · 3/71,816 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000508%

Overall 0.000329% 5/1,520,924 alleles · very rare exomes 4/1,368,778 · genomes 1/152,146 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00418%	23,939
South Asian	0.00135%	73,836
European (non-Finnish)	8.8e-05%	1,136,980

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CFTR
Protein: p.Arg792Ter
Coding: c.2374C>T
MANE Select: NM_000492
dbSNP: rs145449046
Type: single nucleotide variant
Location: chr7:117592541 (GRCh38)
Gene constraint: LOEUF 1.152 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 60 PDB
Residue 792: a UniProt-annotated variant site (in cf); a UniProt-annotated variant site (in cbavd; no effect on glycan maturation but decreased channel activity); the 'disordered r region' region

Full CFTR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cystic fibrosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: bronchiectasis with or without elevated sweat chloride 1 congenital bilateral aplasia of vas deferens from CFTR mutation CFTR-related disorder

For Cystic fibrosis (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

CFTR p.Arg792Gln Uncertain significance ★★ ⚠ same residue
CFTR p.Arg792Gly Uncertain significance ★★ ⚠ same residue
CFTR p.Arg792= Likely benign ★ same residue
CFTR p.Arg792Leu Uncertain significance ⚠ same residue
CFTR p.Arg792fs Pathogenic ★ same residue
CFTR c.1585-1G>A Pathogenic ★★★★ same condition
CFTR c.1766+1G>A Pathogenic ★★★★ same condition
CFTR c.2657+5G>A Pathogenic ★★★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cftr-p-arg792ter (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown