Is CLCN6 p.Gln307Pro (c.920A>C) pathogenic?

CLCN6 p.Gln307Pro (c.920A>C) is classified Uncertain significance in CLCN6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-10). AlphaMissense: likely benign (0.2814); Absent from gnomAD v4.1.

How common is CLCN6 p.Gln307Pro (c.920A>C) in the general population?

CLCN6 p.Gln307Pro (c.920A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLCN6 p.Gln307Pro (c.920A>C)?

AlphaMissense predicts likely benign (score 0.2814) — an in-silico prediction, not a clinical call.

CLCN6 p.Gln307Pro

c.920A>C · rs760769936 · VCV2692972

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2814 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2814	likely benign
REVEL	0.762	pathogenic-leaning
SaProt	LLR -7.55	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.7, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 34 kb · p 2.8e-06 · regional, not allelic
Overall
CADD	24.4	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: CLCN6
Protein: p.Gln307Pro
Coding: c.920A>C
MANE Select: NM_001286
dbSNP: rs760769936
Type: single nucleotide variant
Location: chr1:11828185 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.43 · 3 PDB

Full CLCN6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLCN6 p.Gln307His Uncertain significance ★ ⚠ same residue
CLCN6 p.Tyr553Cys Pathogenic ★★ ⚠ same type
CLCN6 p.Ala127Thr Uncertain significance ★★ ⚠ same type
CLCN6 p.Ala144Glu Uncertain significance ★★ ⚠ same type
CLCN6 p.Ala256Val Uncertain significance ★★ ⚠ same type
CLCN6 p.Ala392Val Uncertain significance ★★ ⚠ same type
CLCN6 p.Ala522Thr Uncertain significance ★★ ⚠ same type
CLCN6 p.Ala527Val Uncertain significance ★★ ⚠ same type

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/clcn6-p-gln307pro (accessed [today's date]).

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