Is COL6A3 p.Ser2467= (c.7401G>A) pathogenic?

COL6A3 p.Ser2467= (c.7401G>A) is classified Conflicting classifications of pathogenicity in COL6A3 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-18). Ultra-rare (popmax 0.0329%, mid); Associated with Bethlem myopathy 1A.

What condition is associated with COL6A3 p.Ser2467= (c.7401G>A)?

COL6A3 p.Ser2467= (c.7401G>A) is associated with Bethlem myopathy 1A, collagen 6-related myopathy (ClinVar).

How common is COL6A3 p.Ser2467= (c.7401G>A) in the general population?

COL6A3 p.Ser2467= (c.7401G>A) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

How is Bethlem muscular dystrophy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

COL6A3 p.Ser2467=

c.7401G>A · rs377572272 · VCV166937

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

Bethlem myopathy 1A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -3.7
Overall
CADD	0.182	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0281% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0271%

Overall 0.0244% 394/1,614,054 alleles · ultra-rare exomes 369/1,461,884 · genomes 25/152,170 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
European (non-Finnish)	0.0308%	3,251
Ashkenazi Jewishnot grpmax-eligible	0.0236%	4,229
Remaining individualsnot grpmax-eligible	0.0144%	6,942
Admixed American	0.00833%	12,001
African / African-American	0.00667%	14,984
South Asian	0.00329%	30,361

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.Ser2467=
Coding: c.7401G>A
MANE Select: NM_004369
dbSNP: rs377572272
Type: single nucleotide variant
Location: chr2:237344617 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 2467: an α-helix; the vwfa 11 domain; the 'nonhelical region' region

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

Disease context

Bethlem myopathy 1A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: collagen 6-related myopathy

For Bethlem muscular dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood, Infancy
Prevalence: 1-9 / 1 000 000 (United Kingdom)

Similar variants

COL6A3 p.Ser2467Leu Conflicting classifications of pathogenicity ★ ⚠ 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-ser2467 (accessed [today's date]).

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