Is COL6A5 p.Gln295Pro (c.884A>C) pathogenic?

COL6A5 p.Gln295Pro (c.884A>C) is classified Uncertain significance in COL6A5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.0834); Absent from gnomAD v4.1.

How common is COL6A5 p.Gln295Pro (c.884A>C) in the general population?

COL6A5 p.Gln295Pro (c.884A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL6A5 p.Gln295Pro (c.884A>C)?

AlphaMissense predicts likely benign (score 0.0834) — an in-silico prediction, not a clinical call.

COL6A5 p.Gln295Pro

c.884A>C · VCV4232459

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0834 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0834	likely benign
REVEL	0.292	indeterminate
SaProt	LLR -6.84	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 0.95	GERP -4
Overall
CADD	16.01	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: COL6A5
Protein: p.Gln295Pro
Coding: c.884A>C
MANE Select: NM_001278298
Type: single nucleotide variant
Location: chr3:130379634 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
Structure: AlphaFold pLDDT 70.94
Residue 295: the 'nonhelical region' region; the vwfa 2 domain

Full COL6A5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL6A5 p.Ala2589Thr Benign ★★ same type
COL6A5 p.Asn641His Benign ★★ same type
COL6A5 p.Asp160= Benign ★★ same type
COL6A5 p.Glu2272Ter Benign ★★ same type
COL6A5 p.Lys620= Benign ★★ same type
COL6A5 p.Ser1539Thr Benign ★★ same type
COL6A5 p.Thr572= Benign ★★ same type
COL6A5 p.Val2425Ile Benign ★★ 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/col6a5-p-gln295pro (accessed [today's date]).

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