COL6A2 p.Ala137=
c.411G>A · rs528885146 · VCV499549
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00441%, nfe)
Conditions
2
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 -5.2 | GERP -3.3 |
| Overall | ||
| CADD | 4.854 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00441%
European (non-Finnish) · 52/1,179,962 alleles
Filtering AF
0.00342%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0031%
Overall
0.00353%
57/1,612,694 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00441% | 22,692 |
| South Asian | 0.00329% | 30,360 |
| East Asian | 0.00223% | 44,846 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
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
- COL6A2
- Protein
- p.Ala137=
- Coding
- c.411G>A
- MANE Select
- NM_001849
- dbSNP
- rs528885146
- Type
- single nucleotide variant
- Location
- chr21:46112274 (GRCh38)
- Gene constraint
- LOEUF 0.895 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.58 · 1 PDB
- Residue 137
- the vwfa 1 domain; the 'nonhelical region' region
Similar variants
- COL6A2 p.Ala137Thr Uncertain significance ★★ ⚠ same residue
- COL6A2 p.Ala137Val Uncertain significance ★★ ⚠ same residue
- COL6A2 c.1000-1G>T Pathogenic ★★ same condition
- COL6A2 c.1000-2A>C Pathogenic ★★ same condition
- COL6A2 c.1053+1G>A Pathogenic ★★ same condition
- COL6A2 c.1053+1G>C Pathogenic/Likely pathogenic ★★ same condition
- COL6A2 c.1053+2T>C Pathogenic/Likely pathogenic ★★ same condition
- COL6A2 c.1054-2A>G 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/col6a2-p-ala137 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown