Is COL6A1 p.Arg925Cys (c.2773C>T) pathogenic?

COL6A1 p.Arg925Cys (c.2773C>T) is classified Benign in COL6A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-14). AlphaMissense: likely benign (0.2546); Very rare (popmax 0.00446%, eas); Associated with Bethlem myopathy 1A.

What condition is associated with COL6A1 p.Arg925Cys (c.2773C>T)?

COL6A1 p.Arg925Cys (c.2773C>T) is associated with Bethlem myopathy 1A (ClinVar).

How common is COL6A1 p.Arg925Cys (c.2773C>T) in the general population?

COL6A1 p.Arg925Cys (c.2773C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

How is Bethlem muscular dystrophy inherited?

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

What do computational predictors say about COL6A1 p.Arg925Cys (c.2773C>T)?

AlphaMissense predicts likely benign (score 0.2546) — an in-silico prediction, not a clinical call.

COL6A1 p.Arg925Cys

c.2773C>T · rs779199061 · VCV848915

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2546 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Bethlem myopathy 1A

Computational evidence

Protein change
AlphaMissense	0.2546	likely benign
REVEL	0.407	indeterminate
SaProt	LLR -12.93	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 1.6, phastCons 0.99
Regional constraint	o/e 0.93	unconstrained · MANE · 14 kb · p 0.038 · regional, not allelic
Overall
CADD	24.6	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 0.00446% East Asian · 2/44,878 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00136% 22/1,612,918 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,439
Admixed American	0.00167%	60,002
Finnishnot grpmax-eligible	0.00159%	63,012
European (non-Finnish)	0.00144%	69,409
African / African-American	0.00133%	74,944

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: COL6A1
Protein: p.Arg925Cys
Coding: c.2773C>T
MANE Select: NM_001848
dbSNP: rs779199061
Type: single nucleotide variant
Location: chr21:46003699 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.28 · 1 PDB
Residue 925: the vwfa 3 domain; the 'c-terminal globular domain' region

Full COL6A1 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

For Bethlem muscular dystrophy (Orphanet):

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

Similar variants

COL6A1 c.1002+1G>A Pathogenic ★★ same condition
COL6A1 c.1003-1G>A Pathogenic ★★ same condition
COL6A1 c.1003-2A>C Pathogenic ★★ same condition
COL6A1 c.1003-2A>G Pathogenic ★★ same condition
COL6A1 c.1056+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL6A1 c.1056+1G>C Pathogenic ★★ same condition
COL6A1 c.1056+2T>A Pathogenic/Likely pathogenic ★★ same condition
COL6A1 c.1056+5G>A 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/col6a1-p-arg925cys (accessed [today's date]).

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