Is COL6A3 p.Arg768= (c.2304C>T) pathogenic?

COL6A3 p.Arg768= (c.2304C>T) is classified Likely benign in COL6A3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-04). Ultra-rare (popmax 0.0373%, sas); Associated with Bethlem myopathy 1A.

What condition is associated with COL6A3 p.Arg768= (c.2304C>T)?

COL6A3 p.Arg768= (c.2304C>T) is associated with Bethlem myopathy 1A (ClinVar).

How common is COL6A3 p.Arg768= (c.2304C>T) in the general population?

COL6A3 p.Arg768= (c.2304C>T) is ultra-rare (popmax 0.0373%, sas) (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.Arg768=

c.2304C>T · rs748301065 · VCV2044430

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0373%, sas)

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 -14	GERP -3.1
Overall
CADD	0.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0373% South Asian · 34/91,088 alleles

Filtering AF 0.0274% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.024%

Overall 0.00372% 60/1,614,112 alleles · ultra-rare exomes 57/1,461,890 · genomes 3/152,222 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0373%	2,679
Middle Eastern	0.0329%	3,041
Remaining individualsnot grpmax-eligible	0.0048%	20,829
East Asian	0.00223%	44,896
Admixed American	0.00167%	60,004
Finnishnot grpmax-eligible	0.00156%	64,040
European (non-Finnish)	0.00153%	65,558

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.Arg768=
Coding: c.2304C>T
MANE Select: NM_004369
dbSNP: rs748301065
Type: single nucleotide variant
Location: chr2:237378829 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 768: the 'nonhelical region' region; the vwfa 4 domain

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

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.Arg768Pro Uncertain significance ★★ same residue
COL6A3 p.Arg768Cys Conflicting classifications of pathogenicity ★ same residue
COL6A3 p.Arg768Gly Conflicting classifications of pathogenicity ★ same residue
COL6A3 p.Arg768His 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

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-arg768 (accessed [today's date]).

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