Is COL6A1 p.Pro591= (c.1773G>A) pathogenic?

COL6A1 p.Pro591= (c.1773G>A) is classified Benign in COL6A1 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-01). Common (popmax 10.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with collagen 6-related myopathy.

What condition is associated with COL6A1 p.Pro591= (c.1773G>A)?

COL6A1 p.Pro591= (c.1773G>A) is associated with collagen 6-related myopathy, Bethlem myopathy 1A (ClinVar).

COL6A1 p.Pro591=

Q: How common is COL6A1 p.Pro591= (c.1773G>A) in the general population?

COL6A1 p.Pro591= (c.1773G>A) is common (popmax 10.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1773G>A · rs74852641 · VCV93828

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 10.6%, afr) — too common for a highly-penetrant pathogenic allele

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 -4.5	GERP -2.3
Overall
CADD	1.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.6% African / African-American · 7,907/74,846 alleles

Filtering AF 10.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.3%

Overall 0.999% 16,119/1,613,082 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.6%	9
South Asian	5.76%	17
Ashkenazi Jewishnot grpmax-eligible	2.54%	39
Remaining individualsnot grpmax-eligible	1.44%	70
Middle Eastern	0.842%	119
Admixed American	0.672%	149
East Asian	0.339%	295
European (non-Finnish)	0.0609%	1,641

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.Pro591=
Coding: c.1773G>A
MANE Select: NM_001848
dbSNP: rs74852641
Type: single nucleotide variant
Location: chr21:45999689 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.28 · 1 PDB
Residue 591: the 'triple-helical region' region

Full COL6A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Also linked: Bethlem myopathy 1A

Similar variants

COL6A1 p.Pro591Leu Likely benign ★ same residue
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

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-pro591 (accessed [today's date]).

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