Is COL6A1 p.Pro952= (c.2856C>T) pathogenic?

COL6A1 p.Pro952= (c.2856C>T) is classified Conflicting classifications of pathogenicity in COL6A1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-14). Ultra-rare (popmax 0.0472%, sas); Associated with collagen 6-related myopathy.

What condition is associated with COL6A1 p.Pro952= (c.2856C>T)?

COL6A1 p.Pro952= (c.2856C>T) is associated with collagen 6-related myopathy, Bethlem myopathy 1A (ClinVar).

How common is COL6A1 p.Pro952= (c.2856C>T) in the general population?

COL6A1 p.Pro952= (c.2856C>T) is ultra-rare (popmax 0.0472%, sas) (gnomAD).

COL6A1 p.Pro952=

c.2856C>T · rs140427635 · VCV285248

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0472%, sas)

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 -6.7	GERP -3.2
Overall
CADD	0.977	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0472% South Asian · 43/91,066 alleles

Filtering AF 0.036% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0321%

Overall 0.0212% 341/1,611,748 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0636%	1,572
South Asiangrpmax	0.0472%	2,118
Remaining individualsnot grpmax-eligible	0.0416%	2,401
Admixed American	0.0183%	5,454
European (non-Finnish)	0.018%	5,561
Middle Eastern	0.0165%	6,060
East Asian	0.00669%	14,945
African / African-American	0.00666%	15,008

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro952=
Coding: c.2856C>T
MANE Select: NM_001848
dbSNP: rs140427635
Type: single nucleotide variant
Location: chr21:46003782 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.28 · 1 PDB
Residue 952: the vwfa 3 domain; the 'c-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.Pro952Leu 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
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-pro952 (accessed [today's date]).

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