Is COL6A3 p.Phe377= (c.1131C>T) pathogenic?

COL6A3 p.Phe377= (c.1131C>T) is classified Conflicting classifications of pathogenicity in COL6A3 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-10-29). Rare (popmax 0.108%, afr); Associated with collagen 6-related myopathy.

What condition is associated with COL6A3 p.Phe377= (c.1131C>T)?

COL6A3 p.Phe377= (c.1131C>T) is associated with collagen 6-related myopathy, Bethlem myopathy 1A (ClinVar).

How common is COL6A3 p.Phe377= (c.1131C>T) in the general population?

COL6A3 p.Phe377= (c.1131C>T) is rare (popmax 0.108%, afr) (gnomAD).

COL6A3 p.Phe377=

c.1131C>T · rs189772397 · VCV291211

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.108%, afr)

Conditions

collagen 6-related myopathy

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 0.093	GERP -0.76, phastCons 0.013
Overall
CADD	11.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.108% African / African-American · 81/75,044 alleles

Filtering AF 0.0889% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.082%

Overall 0.0096% 155/1,613,960 alleles · rare exomes 101/1,461,646 · genomes 54/152,314 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.108%	926
Remaining individualsnot grpmax-eligible	0.016%	6,250
Admixed American	0.00833%	12,001
European (non-Finnish)	0.00475%	21,071
East Asian	0.00223%	44,870
South Asian	0.0022%	45,503

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.Phe377=
Coding: c.1131C>T
MANE Select: NM_004369
dbSNP: rs189772397
Type: single nucleotide variant
Location: chr2:237387763 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 377: the 'nonhelical region' region; the vwfa 2 domain

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.Phe377Leu 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-phe377 (accessed [today's date]).

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