COL6A2 p.Pro423=
c.1269G>C · rs144136807 · VCV290928
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 0.0374%, afr)
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 -2.7 |
| Overall | ||
| CADD | 0.012 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0374%
African / African-American · 28/74,826 alleles
Filtering AF
0.0266%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0229%
Overall
0.00205%
33/1,609,152 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0374% | 2,672 |
| Admixed American | 0.00502% | 19,931 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,105 |
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.Pro423=
- Coding
- c.1269G>C
- MANE Select
- NM_001849
- dbSNP
- rs144136807
- Type
- single nucleotide variant
- Location
- chr21:46119119 (GRCh38)
- Gene constraint
- LOEUF 0.895 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.58 · 1 PDB
- Residue 423
- the 'triple-helical region' region; the 'disordered' region
Similar variants
- COL6A2 p.Pro423Leu 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
- COL6A2 c.115+2T>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-pro423 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown