Is COL6A3 p.Pro970Arg (c.2909C>G) pathogenic?

COL6A3 p.Pro970Arg (c.2909C>G) is classified Uncertain significance in COL6A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-08-26). AlphaMissense: likely pathogenic (0.7266); Absent from gnomAD v4.1.

How common is COL6A3 p.Pro970Arg (c.2909C>G) in the general population?

COL6A3 p.Pro970Arg (c.2909C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL6A3 p.Pro970Arg (c.2909C>G)?

AlphaMissense predicts likely pathogenic (score 0.7266) — an in-silico prediction, not a clinical call.

COL6A3 p.Pro970Arg

c.2909C>G · rs886044591 · VCV290932

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7266 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.7266	likely pathogenic
REVEL	0.588	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 28 kb · p 0.26 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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: COL6A3
Protein: p.Pro970Arg
Coding: c.2909C>G
MANE Select: NM_004369
dbSNP: rs886044591
Type: single nucleotide variant
Location: chr2:237376933 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 970: the 'nonhelical region' region; the vwfa 5 domain

Full COL6A3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL6A3 p.Pro970Ala Uncertain significance ★ same residue
COL6A3 p.Pro970Ser Uncertain significance ★ same residue
COL6A3 c.3071-2A>G Likely pathogenic ★★ same type
COL6A3 c.5838+1G>T Pathogenic/Likely pathogenic ★★ same type
COL6A3 c.6156+1G>A Pathogenic ★★ same type
COL6A3 c.6157-2A>C Pathogenic ★★ same type
COL6A3 c.6210+1G>A Pathogenic ★★ same type
COL6A3 c.6282+1G>A Pathogenic ★★ 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/col6a3-p-pro970arg (accessed [today's date]).

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