COL2A1 p.Gly499=
c.1497C>T · rs773764091 · VCV1094576
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0402%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>C here scores Δ0.29 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.56 | GERP -3.8 |
| Overall | ||
| CADD | 2.56 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0402%
East Asian · 17/42,334 alleles
Filtering AF
0.0255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.021%
Overall
0.00178%
28/1,569,294 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0402% | 2,490 |
| African / African-American | 0.00136% | 73,774 |
| European (non-Finnish) | 0.000865% | 115,655 |
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.Gly499=
- Coding
- c.1497C>T
- MANE Select
- NM_001844
- dbSNP
- rs773764091
- Type
- single nucleotide variant
- Location
- chr12:47986366 (GRCh38)
- Gene constraint
- LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 53.56 · 11 PDB
- Residue 499
- the 'disordered' region; the 'triple-helical region' region
Similar variants
- COL2A1 c.1023+1G>A Pathogenic ★★ same type
- COL2A1 c.1024-2A>C Pathogenic ★★ same type
- COL2A1 c.1069-2A>G Pathogenic/Likely pathogenic ★★ same type
- COL2A1 c.1221+1G>A Pathogenic ★★ same type
- COL2A1 c.1222-2A>G Pathogenic ★★ same type
- COL2A1 c.1365+1G>A Pathogenic/Likely pathogenic ★★ same type
- COL2A1 c.1420-1G>A Pathogenic ★★ same type
- COL2A1 c.1420-2A>G Pathogenic/Likely pathogenic ★★ same type
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-gly499 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown