Is CFTR p.Val232Asp (c.695T>A) pathogenic?

CFTR p.Val232Asp (c.695T>A) is classified Pathogenic in CFTR (ClinVar, Expert panel, 19 submitters; last evaluated 2018-08-31). AlphaMissense: likely pathogenic (0.885); Very rare (popmax 0.00834%, amr); Associated with cystic fibrosis.

What condition is associated with CFTR p.Val232Asp (c.695T>A)?

CFTR p.Val232Asp (c.695T>A) is associated with cystic fibrosis, hereditary chronic pancreatitis, bronchiectasis with or without elevated sweat chloride 1 (ClinVar).

How common is CFTR p.Val232Asp (c.695T>A) in the general population?

CFTR p.Val232Asp (c.695T>A) is very rare (popmax 0.00834%, amr) (gnomAD).

How is Cystic fibrosis inherited?

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

What do computational predictors say about CFTR p.Val232Asp (c.695T>A)?

AlphaMissense predicts likely pathogenic (score 0.885) — an in-silico prediction, not a clinical call.

CFTR p.Val232Asp

c.695T>A · rs397508783 · VCV54041

Pathogenic Expert panel

Classification

Pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 19 submitters

AlphaMissense

likely pathogenic

0.885 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cystic fibrosis

Computational evidence

Protein change
AlphaMissense	0.885	likely pathogenic ✓ concordant with ClinVar
REVEL	0.72	pathogenic-leaning
SaProt	LLR -14.12	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.4, phastCons 0.99
Regional constraint	o/e 1.13	unconstrained · MANE · 187 kb · p 2.1e-08 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00834% Admixed American · 5/59,972 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00192% 31/1,613,966 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,994
European (non-Finnish)	0.00212%	47,201
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Val232Asp
Coding: c.695T>A
MANE Select: NM_000492
dbSNP: rs397508783
Type: single nucleotide variant
Location: chr7:117535363 (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 232: a UniProt-annotated variant site (in cf); a UniProt-annotated variant site (in cbavd); 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

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

Also linked: hereditary chronic pancreatitis 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.Val232= Likely benign ★★ 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
CFTR c.2988+1G>A Pathogenic ★★★★ same condition
CFTR c.3718-2477C>T Pathogenic ★★★★ same condition
CFTR c.489+1G>T Pathogenic ★★★★ same condition
CFTR c.579+1G>T 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-val232asp (accessed [today's date]).

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