COL6A2 p.Pro28=
c.84G>A · rs140890046 · VCV283330
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0583%, amr)
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 -20 | GERP -3.2 |
| Overall | ||
| CADD | 0.01 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0583%
Admixed American · 35/59,996 alleles
Filtering AF
0.0431%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0378%
Overall
0.017%
274/1,612,710 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0583% | 1,714 |
| African / African-American | 0.02% | 4,992 |
| European (non-Finnish) | 0.0176% | 5,673 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,941 |
| Finnishnot grpmax-eligible | 0.00636% | 15,730 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,600 |
| East Asian | 0.00223% | 44,878 |
| South Asian | 0.0011% | 91,066 |
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.Pro28=
- Coding
- c.84G>A
- MANE Select
- NM_001849
- dbSNP
- rs140890046
- Type
- single nucleotide variant
- Location
- chr21:46111560 (GRCh38)
- Gene constraint
- LOEUF 0.895 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.58 · 1 PDB
- Residue 28
- the 'nonhelical region' region
Similar variants
- COL6A2 p.Pro28Ser Uncertain significance ★★ ⚠ same residue
- COL6A2 p.Pro28Arg Uncertain significance ★ ⚠ same residue
- COL6A2 p.Pro28Leu Likely benign ★ same residue
- COL6A2 p.Pro28Ala 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
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-pro28 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown