Is COL6A3 p.Val1069Met (c.3205G>A) pathogenic?

COL6A3 p.Val1069Met (c.3205G>A) is classified Conflicting classifications of pathogenicity in COL6A3 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.2137); Rare (popmax 0.607%, eas); Associated with Inborn genetic diseases.

What condition is associated with COL6A3 p.Val1069Met (c.3205G>A)?

COL6A3 p.Val1069Met (c.3205G>A) is associated with Inborn genetic diseases, Bethlem myopathy 1A, collagen 6-related myopathy (ClinVar).

How common is COL6A3 p.Val1069Met (c.3205G>A) in the general population?

COL6A3 p.Val1069Met (c.3205G>A) is rare (popmax 0.607%, eas) (gnomAD).

What do computational predictors say about COL6A3 p.Val1069Met (c.3205G>A)?

AlphaMissense predicts likely benign (score 0.2137) — an in-silico prediction, not a clinical call.

COL6A3 p.Val1069Met

c.3205G>A · rs115297652 · VCV285464

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2137 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.607%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2137	likely benign
REVEL	0.362	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.28	GERP -3.7
Regional constraint	o/e 0.97	unconstrained · MANE · 28 kb · p 0.26 · regional, not allelic
Overall
CADD	19.92	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

Grpmax group 0.607% East Asian · 272/44,820 alleles

Filtering AF 0.548% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.525%

Overall 0.0204% 330/1,613,910 alleles · rare exomes 303/1,461,832 · genomes 27/152,078 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.607%	165
Remaining individualsnot grpmax-eligible	0.0448%	2,232
South Asian	0.00439%	22,767
African / African-American	0.00267%	37,488
European (non-Finnish)	0.00203%	49,167

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.Val1069Met
Coding: c.3205G>A
MANE Select: NM_004369
dbSNP: rs115297652
Type: single nucleotide variant
Location: chr2:237374886 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 1069: the 'nonhelical region' region; the vwfa 6 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bethlem myopathy 1A collagen 6-related myopathy

Similar variants

COL6A3 c.5838+1G>T Pathogenic/Likely pathogenic ★★ same condition
COL6A3 c.6156+1G>A Pathogenic ★★ same condition
COL6A3 c.6157-2A>C Pathogenic ★★ same condition
COL6A3 c.6210+1G>A Pathogenic ★★ same condition
COL6A3 c.6282+1G>A Pathogenic ★★ same condition
COL6A3 c.6282+1G>C Pathogenic/Likely pathogenic ★★ same condition
COL6A3 c.6309+1G>A Pathogenic ★★ same condition
COL6A3 c.6309+1G>T Pathogenic/Likely 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/col6a3-p-val1069met (accessed [today's date]).

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