Is COL6A1 p.Asp729= (c.2187C>T) pathogenic?

COL6A1 p.Asp729= (c.2187C>T) is classified Conflicting classifications of pathogenicity in COL6A1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-11-11). Rare (popmax 0.1%, afr); Associated with Bethlem myopathy 1A.

What condition is associated with COL6A1 p.Asp729= (c.2187C>T)?

COL6A1 p.Asp729= (c.2187C>T) is associated with Bethlem myopathy 1A (ClinVar).

How common is COL6A1 p.Asp729= (c.2187C>T) in the general population?

COL6A1 p.Asp729= (c.2187C>T) is rare (popmax 0.1%, afr) (gnomAD).

How is Bethlem muscular dystrophy inherited?

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

COL6A1 p.Asp729=

c.2187C>T · rs369502543 · VCV508782

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.1%, afr)

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
Overall
CADD	6.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.1% African / African-American · 75/74,662 alleles

Filtering AF 0.0821% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0754%

Overall 0.00528% 84/1,591,478 alleles · rare exomes 37/1,439,130 · genomes 47/152,348 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.1%	995
Admixed American	0.00178%	56,256
Remaining individualsnot grpmax-eligible	0.00162%	61,672
South Asian	0.00113%	88,604
European (non-Finnish)	0.000513%	194,999

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.Asp729=
Coding: c.2187C>T
MANE Select: NM_001848
dbSNP: rs369502543
Type: single nucleotide variant
Location: chr21:46002338 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.28 · 1 PDB
Residue 729: the vwfa 2 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-asp729 (accessed [today's date]).

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