Is COL6A1 p.Pro193= (c.579C>T) pathogenic?

COL6A1 p.Pro193= (c.579C>T) is classified Benign/Likely benign in COL6A1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-27). Low-frequency (popmax 1.62%, afr); Associated with collagen 6-related myopathy.

What condition is associated with COL6A1 p.Pro193= (c.579C>T)?

COL6A1 p.Pro193= (c.579C>T) is associated with collagen 6-related myopathy, Bethlem myopathy 1A (ClinVar).

How common is COL6A1 p.Pro193= (c.579C>T) in the general population?

COL6A1 p.Pro193= (c.579C>T) is low-frequency (popmax 1.62%, afr) (gnomAD).

COL6A1 p.Pro193=

c.579C>T · rs61751027 · VCV258303

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.62%, afr)

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 -20	GERP -2.1
Overall
CADD	0.061	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.62% African / African-American · 1,174/72,548 alleles

Filtering AF 1.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.51%

Overall 0.0893% 1,381/1,547,322 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.62%	62
Middle Eastern	0.206%	484
Remaining individualsnot grpmax-eligible	0.125%	801
Admixed American	0.117%	851
European (non-Finnish)	0.00514%	19,439
South Asian	0.00119%	83,998

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.Pro193=
Coding: c.579C>T
MANE Select: NM_001848
dbSNP: rs61751027
Type: single nucleotide variant
Location: chr21:45986676 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.28 · 1 PDB
Residue 193: the vwfa 1 domain; the 'n-terminal globular domain' 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.Pro193Ala Uncertain significance ★ ⚠ same residue
COL6A1 p.Pro193Ser Uncertain significance ★ ⚠ 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

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-pro193 (accessed [today's date]).

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