Is COL6A3 p.Ala1965Pro (c.5893G>C) pathogenic?

COL6A3 p.Ala1965Pro (c.5893G>C) is classified Uncertain significance in COL6A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-31). AlphaMissense: likely pathogenic (0.8633); Very rare (popmax 0.00133%, afr).

How common is COL6A3 p.Ala1965Pro (c.5893G>C) in the general population?

COL6A3 p.Ala1965Pro (c.5893G>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about COL6A3 p.Ala1965Pro (c.5893G>C)?

AlphaMissense predicts likely pathogenic (score 0.8633) — an in-silico prediction, not a clinical call.

COL6A3 p.Ala1965Pro

c.5893G>C · rs1364239110 · VCV595937

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8633 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.8633	likely pathogenic
REVEL	0.228	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 0.52, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 6,991 bp · p 0.73 · regional, not allelic
Overall
CADD	21.4	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

Grpmax group 0.00133% African / African-American · 1/74,924 alleles

Overall 0.000657% 1/152,202 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: COL6A3
Protein: p.Ala1965Pro
Coding: c.5893G>C
MANE Select: NM_004369
dbSNP: rs1364239110
Type: single nucleotide variant
Location: chr2:237364374 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 1965: the vwfa 10 domain; the 'nonhelical region' region

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

Similar variants

COL6A3 p.Ala1965Thr Uncertain significance ★★ ⚠ same residue
COL6A3 p.Ala1965= Likely benign ★ 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-ala1965pro (accessed [today's date]).

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