Is CFTR p.Pro439Ala (c.1315C>G) pathogenic?

CFTR p.Pro439Ala (c.1315C>G) is classified Uncertain significance in CFTR (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.0969); Absent from gnomAD v4.1; Associated with CFTR-related disorder.

What condition is associated with CFTR p.Pro439Ala (c.1315C>G)?

CFTR p.Pro439Ala (c.1315C>G) is associated with CFTR-related disorder (ClinVar).

How common is CFTR p.Pro439Ala (c.1315C>G) in the general population?

CFTR p.Pro439Ala (c.1315C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFTR p.Pro439Ala (c.1315C>G)?

AlphaMissense predicts likely benign (score 0.0969) — an in-silico prediction, not a clinical call.

CFTR p.Pro439Ala

c.1315C>G · rs397508187 · VCV910201

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0969 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CFTR-related disorder

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0969	likely benign
REVEL	0.752	pathogenic-leaning
SaProt	LLR -7.49	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.7	GERP 0.5, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 187 kb · p 2.1e-08 · regional, not allelic
Overall
CADD	24.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CFTR
Protein: p.Pro439Ala
Coding: c.1315C>G
MANE Select: NM_000492
dbSNP: rs397508187
Type: single nucleotide variant
Location: chr7:117548746 (GRCh38)

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

Disease context

CFTR-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-pro439ala (accessed [today's date]).

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