COL2A1 p.Asp1469=
c.4407C>T · rs750477616 · VCV516290
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0307%, sas)
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 8.7 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 9.427 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0307%
South Asian · 28/91,082 alleles
Filtering AF
0.0218%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0188%
Overall
0.00421%
68/1,614,002 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0307% | 3,253 |
| Middle Eastern | 0.0164% | 6,084 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,622 |
| European (non-Finnish) | 0.00288% | 34,707 |
| African / African-American | 0.00134% | 74,872 |
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.Asp1469=
- Coding
- c.4407C>T
- MANE Select
- NM_001844
- dbSNP
- rs750477616
- Type
- single nucleotide variant
- Location
- chr12:47973464 (GRCh38)
- Gene constraint
- LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 53.56 · 11 PDB
- Residue 1469
- a UniProt-annotated variant site (in plsd-t); the fibrillar collagen nc1 domain; a disulfide bond
Similar variants
- COL2A1 p.Asp1469Tyr 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
- 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-asp1469 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown