COL2A1 p.Pro337=
c.1011T>C · rs761001588 · VCV798266
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0417%, amr)
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 0.019 | GERP -0.38, phastCons 0.021 |
| Overall | ||
| CADD | 9.233 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0417%
Admixed American · 25/60,010 alleles
Filtering AF
0.0289%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0247%
Overall
0.00192%
31/1,614,102 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0417% | 2,400 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| European (non-Finnish) | 0.000254% | 393,345 |
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.Pro337=
- Coding
- c.1011T>C
- MANE Select
- NM_001844
- dbSNP
- rs761001588
- Type
- single nucleotide variant
- Location
- chr12:47992890 (GRCh38)
- Gene constraint
- LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 53.56 · 11 PDB
- Residue 337
- the 'disordered' region; the 'triple-helical region' region
Similar variants
- COL2A1 p.Pro337Ser Likely benign ★ same residue
- 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
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-pro337 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown