Is COL6A1 p.Pro9= (c.27C>G) pathogenic?

COL6A1 p.Pro9= (c.27C>G) is classified Benign in COL6A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-18). Very rare (popmax 0.0068%, amr); Associated with Bethlem myopathy 1A.

What condition is associated with COL6A1 p.Pro9= (c.27C>G)?

COL6A1 p.Pro9= (c.27C>G) is associated with Bethlem myopathy 1A (ClinVar).

How common is COL6A1 p.Pro9= (c.27C>G) in the general population?

COL6A1 p.Pro9= (c.27C>G) is very rare (popmax 0.0068%, amr) (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.Pro9=

c.27C>G · rs747094652 · VCV2920525

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0068%, amr)

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 0.012	GERP 0.081, phastCons 0.001
Overall
CADD	7.945	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0068% Admixed American · 4/58,830 alleles

Filtering AF 0.00229% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.000483% 7/1,448,732 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0068%	14,708
European (non-Finnish)	0.000255%	391,676

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.Pro9=
Coding: c.27C>G
MANE Select: NM_001848
dbSNP: rs747094652
Type: single nucleotide variant
Location: chr21:45981877 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.28 · 1 PDB

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-pro9 (accessed [today's date]).

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