COL2A1 p.Arg653=
c.1957C>A · rs121912893 · VCV2125060
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.54e-05%, nfe)
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 6.4 | GERP 0.83, phastCons 1 |
| Overall | ||
| CADD | 12.88 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.54e-05%
European (non-Finnish) · 1/1,170,816 alleles
Overall
6.27e-05%
1/1,595,110 alleles · very rare
exomes 1/1,442,782 · genomes 0/152,328 · joint denominator
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.Arg653=
- Coding
- c.1957C>A
- MANE Select
- NM_001844
- dbSNP
- rs121912893
- Type
- single nucleotide variant
- Location
- chr12:47983721 (GRCh38)
- Gene constraint
- LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 53.56 · 11 PDB
- Residue 653
- the 'disordered' region; the 'triple-helical region' region
Similar variants
- COL2A1 p.Arg653Ter Pathogenic ★★ same residue
- COL2A1 p.Arg653Gln Uncertain significance ★★ same residue
- COL2A1 p.Arg653Leu Uncertain significance ★★ ⚠ same residue
- COL2A1 p.Arg653fs Pathogenic ★ 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
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-arg653 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown