COL2A1 p.Pro794=
c.2382T>A · rs373352689 · VCV1383662
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0273%, afr)
Conditions
1
COL2A1-related disorder
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 -0.45 | GERP -3.5 |
| Overall | ||
| CADD | 8.21 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0273%
African / African-American · 20/73,160 alleles
Filtering AF
0.0181%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0151%
Overall
0.00142%
22/1,554,484 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0273% | 3,658 |
| Remaining individualsnot grpmax-eligible | 0.00332% | 30,130 |
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
- COL2A1
- Protein
- p.Pro794=
- Coding
- c.2382T>A
- MANE Select
- NM_001844
- dbSNP
- rs373352689
- Type
- single nucleotide variant
- Location
- chr12:47981803 (GRCh38)
- Gene constraint
- LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 53.56 · 11 PDB
- Residue 794
- the 'disordered' region; the 'triple-helical region' region
Disease context
COL2A1-related disorder
Similar variants
- COL2A1 p.Pro794Arg Uncertain significance ★★ ⚠ same residue
- COL2A1 p.Pro794Leu Uncertain significance ★★ ⚠ same residue
- COL2A1 p.Pro794Ser Uncertain significance ★★ ⚠ same residue
- COL2A1 p.Pro794Ala Uncertain significance ★ ⚠ same residue
- COL2A1 c.1024-2A>C Pathogenic ★★ same condition
- COL2A1 c.1069-2A>G Pathogenic/Likely pathogenic ★★ same condition
- COL2A1 c.1527+135G>A Pathogenic/Likely pathogenic ★★ same condition
- COL2A1 c.1681-2A>G 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/col2a1-p-pro794 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown