Is CFTR p.Gln685Pro (c.2054A>C) pathogenic?

CFTR p.Gln685Pro (c.2054A>C) is classified Uncertain significance in CFTR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-22). AlphaMissense: likely benign (0.0621); Absent from gnomAD v4.1; Associated with cystic fibrosis.

What condition is associated with CFTR p.Gln685Pro (c.2054A>C)?

CFTR p.Gln685Pro (c.2054A>C) is associated with cystic fibrosis (ClinVar).

How common is CFTR p.Gln685Pro (c.2054A>C) in the general population?

CFTR p.Gln685Pro (c.2054A>C) is absent from gnomAD v4.1 (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.Gln685Pro (c.2054A>C)?

AlphaMissense predicts likely benign (score 0.0621) — an in-silico prediction, not a clinical call.

CFTR p.Gln685Pro

c.2054A>C · rs2485109834 · VCV2453627

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0621 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

cystic fibrosis

Computational evidence

Protein change
AlphaMissense	0.0621	likely benign
REVEL	0.405	indeterminate
SaProt	LLR -5.84	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.7, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 187 kb · p 2.1e-08 · regional, not allelic
Overall
CADD	17.02	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Gln685Pro
Coding: c.2054A>C
MANE Select: NM_000492
dbSNP: rs2485109834
Type: single nucleotide variant
Location: chr7:117592221 (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 685: 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

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

For Cystic fibrosis (Orphanet):

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

Similar variants

CFTR p.Gln685Ter Pathogenic ★★★ same residue
CFTR p.Gln685= Conflicting classifications of pathogenicity ★ same residue
CFTR p.Gln685Lys Uncertain significance ★ ⚠ same residue
CFTR p.Gln685fs 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
CFTR c.2988+1G>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-gln685pro (accessed [today's date]).

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