Is CFTR p.Phe131fs (c.393del) pathogenic?

CFTR p.Phe131fs (c.393del) is classified Pathogenic in CFTR (ClinVar, Single submitter, 2 submitters; last evaluated 2024-04-25). Absent from gnomAD; Associated with CFTR-related disorder.

What condition is associated with CFTR p.Phe131fs (c.393del)?

CFTR p.Phe131fs (c.393del) is associated with CFTR-related disorder, cystic fibrosis (ClinVar).

How common is CFTR p.Phe131fs (c.393del) in the general population?

CFTR p.Phe131fs (c.393del) is absent from gnomAD (gnomAD).

CFTR p.Phe131fs

c.393del · rs397508647 · VCV53859

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 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 4 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.8	GERP -3.8

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.Phe131fs
Coding: c.393del
MANE Select: NM_000492
dbSNP: rs397508647
Type: Deletion
Location: chr7:117531016 (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 131: the abc transmembrane type-1 1 domain; an α-helix

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

Disease context

Also linked: cystic fibrosis

Similar variants

CFTR p.Phe131= Conflicting classifications of pathogenicity ★ same residue
CFTR p.Phe131Leu Uncertain significance ★ ⚠ same residue
CFTR p.Phe131Tyr Uncertain significance ★ ⚠ same residue
CFTR p.Lys1177fs Pathogenic ★★★★ same condition
CFTR c.(?_1 Pathogenic ★★★ same condition
CFTR c.1211del Pathogenic ★★★ same condition
CFTR c.(1584+1_1585-1 Pathogenic ★★★ same condition
CFTR c.(164+1_165-1 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-phe131fs (accessed [today's date]).

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