COL2A1 p.Gln221Pro
c.662A>C · rs368187891 · VCV842038
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1268 | likely benign |
|---|---|---|
| REVEL | 0.641 | indeterminate |
| SaProt | LLR -5.86 | tolerated |
| ⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>A here scores Δ0.26 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.62 | unconstrained · MANE · 21 kb · p 2.4e-45 · regional, not allelic |
| Overall | ||
| CADD | 23.9 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0211% | 4,739 |
| Admixed American | 0.015% | 6,665 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,414 |
| Finnishnot grpmax-eligible | 0.00469% | 21,334 |
| African / African-American | 0.00267% | 37,429 |
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.Gln221Pro
- Coding
- c.662A>C
- MANE Select
- NM_001844
- dbSNP
- rs368187891
- Type
- single nucleotide variant
- Location
- chr12:47995756 (GRCh38)
- Gene constraint
- LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 53.56 · 11 PDB
- Residue 221
- the 'disordered' region; the 'triple-helical region' region
Similar variants
- COL2A1 p.Gln221Ter Conflicting classifications of pathogenicity ★ ⚠ same residue
- COL2A1 p.Gln221= Likely benign ★ same residue
- COL2A1 p.Cys52Ter Pathogenic/Likely pathogenic ★★ same condition
- COL2A1 p.Gln39Ter Pathogenic ★★ same condition
- COL2A1 p.Gly546Ser Pathogenic/Likely pathogenic ★★ same condition
- COL2A1 p.Gly930Asp Likely pathogenic ★★ same condition
- COL2A1 p.Ala1093Val Uncertain significance ★★ ⚠ same condition
- COL2A1 p.Ala180Thr Uncertain significance ★★ ⚠ 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-gln221pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown