Is CFTR p.Arg697fs (c.2089dup) pathogenic?

CFTR p.Arg697fs (c.2089dup) is classified Pathogenic in CFTR (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-03-09). Absent from gnomAD; Associated with CFTR-related disorder.

What condition is associated with CFTR p.Arg697fs (c.2089dup)?

CFTR p.Arg697fs (c.2089dup) is associated with CFTR-related disorder, bronchiectasis with or without elevated sweat chloride 1, cystic fibrosis (ClinVar).

How common is CFTR p.Arg697fs (c.2089dup) in the general population?

CFTR p.Arg697fs (c.2089dup) is absent from gnomAD (gnomAD).

CFTR p.Arg697fs

c.2089dup · rs397508341 · VCV53439

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

CFTR-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 14 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CFTR
Protein: p.Arg697fs
Coding: c.2089dup
MANE Select: NM_000492
dbSNP: rs397508341
Type: Duplication
Location: chr7:117592250 (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 697: a UniProt-annotated variant site (in cf); the 'disordered r region' region

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

Disease context

Also linked: bronchiectasis with or without elevated sweat chloride 1 cystic fibrosis

Similar variants

CFTR p.Arg697Thr Uncertain significance ★ ⚠ same residue
CFTR c.164+4dup Pathogenic ★★★ same condition
CFTR c.3468+2dup Pathogenic ★★★ same condition
CFTR p.Arg1301Ter Pathogenic ★★★ same condition
CFTR p.Arg59fs Pathogenic ★★★ same condition
CFTR p.Asp835Ter Pathogenic ★★★ same condition
CFTR p.Gln378fs Pathogenic ★★★ same condition
CFTR p.Gln685fs 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-arg697fs (accessed [today's date]).

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