COL6A2 p.Ala884Thr
c.2650G>A · VCV3770707
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.212%, sas)
Conditions
1
collagen 6-related myopathy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.359 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 6.9 | GERP 0.26, phastCons 1 |
| Regional constraint | o/e 1.16 | unconstrained · MANE · 16 kb · p 1.4e-07 · regional, not allelic |
| Overall | ||
| CADD | 22.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.212%
South Asian · 193/91,068 alleles
Filtering AF
0.187%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.178%
Overall
0.0141%
227/1,613,002 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.212% | 472 |
| Middle Eastern | 0.0165% | 6,062 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,414 |
| African / African-American | 0.00533% | 18,768 |
| European (non-Finnish) | 0.00186% | 53,633 |
| Admixed American | 0.00167% | 60,004 |
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.Ala884Thr
- Coding
- c.2650G>A
- MANE Select
- NM_001849 · reported on NM_058174
- Type
- single nucleotide variant
- Location
- chr21:46129384 (GRCh38)
- Gene constraint
- LOEUF 0.895 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.58 · 1 PDB
- Residue 884
- the vwfa 3 domain; a β-strand; the 'nonhelical region' region
Similar variants
- COL6A2 p.Ala884Val Uncertain significance same residue
- COL6A2 c.1053+1G>C Pathogenic/Likely pathogenic ★★ same condition
- COL6A2 c.115+2T>C Pathogenic/Likely pathogenic ★★ same condition
- COL6A2 c.1970-9G>A Pathogenic/Likely pathogenic ★★ same condition
- COL6A2 p.Arg876His Likely pathogenic ★★ ⚠ same condition
- COL6A2 p.Asp871Asn Pathogenic/Likely pathogenic ★★ ⚠ same condition
- COL6A2 p.Gln858Ter Pathogenic/Likely pathogenic ★★ same condition
- COL6A2 c.*203G>A Uncertain significance ★★ 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-ala884thr (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown