Is COL6A3 p.Ala830Ser (c.2488G>T) pathogenic?

COL6A3 p.Ala830Ser (c.2488G>T) is classified Benign in COL6A3 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0751); Common (popmax 9.38%, amr) — too common for a highly-penetrant pathogenic allele; Associated with collagen 6-related myopathy.

What condition is associated with COL6A3 p.Ala830Ser (c.2488G>T)?

COL6A3 p.Ala830Ser (c.2488G>T) is associated with collagen 6-related myopathy, Bethlem myopathy 1A (ClinVar).

What do computational predictors say about COL6A3 p.Ala830Ser (c.2488G>T)?

AlphaMissense predicts likely benign (score 0.0751) — an in-silico prediction, not a clinical call.

COL6A3 p.Ala830Ser

Q: How common is COL6A3 p.Ala830Ser (c.2488G>T) in the general population?

COL6A3 p.Ala830Ser (c.2488G>T) is common (popmax 9.38%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2488G>T · rs77181645 · VCV94916

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

AlphaMissense

likely benign

0.0751 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 9.38%, amr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

collagen 6-related myopathy

Computational evidence

Protein change
AlphaMissense	0.0751	likely benign
REVEL	0.081	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -3.1
Regional constraint	o/e 0.97	unconstrained · MANE · 28 kb · p 0.26 · regional, not allelic
Overall
CADD	12.44	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 9.38% Admixed American · 5,630/60,016 alleles

Filtering AF 9.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.09%

Overall 0.885% 14,266/1,612,522 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	9.38%	11
East Asian	4.83%	21
South Asian	3.18%	31
Finnishnot grpmax-eligible	2.78%	36
Remaining individualsnot grpmax-eligible	1.07%	94
African / African-American	0.207%	484
Ashkenazi Jewishnot grpmax-eligible	0.115%	871
European (non-Finnish)	0.0789%	1,267
Middle Eastern	0.0634%	1,577

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.Ala830Ser
Coding: c.2488G>T
MANE Select: NM_004369
dbSNP: rs77181645
Type: single nucleotide variant
Location: chr2:237378645 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 830: the 'nonhelical region' region; a UniProt-annotated variant site (in)

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

Disease context

Also linked: Bethlem myopathy 1A

Similar variants

COL6A3 p.Ala830Thr Uncertain significance ★★ ⚠ same residue
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

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-ala830ser (accessed [today's date]).

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