COL2A1 p.Cys1323=
c.3969C>T · rs577585827 · VCV390559
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0198%, 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 -5.1 | GERP -1.4 |
| Overall | ||
| CADD | 10.67 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0198%
South Asian · 18/91,082 alleles
Filtering AF
0.017%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0162%
Overall
0.0165%
266/1,614,184 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0198% | 5,060 |
| European (non-Finnish) | 0.0191% | 5,245 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,683 |
| Admixed American | 0.0117% | 8,574 |
| African / African-American | 0.004% | 25,011 |
| East Asian | 0.00223% | 44,882 |
| Finnishnot grpmax-eligible | 0.00156% | 64,032 |
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.Cys1323=
- Coding
- c.3969C>T
- MANE Select
- NM_001844
- dbSNP
- rs577585827
- Type
- single nucleotide variant
- Location
- chr12:47974780 (GRCh38)
- Gene constraint
- LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 53.56 · 11 PDB
- Residue 1323
- the fibrillar collagen nc1 domain; a disulfide bond
Similar variants
- COL2A1 p.Cys1323Ter Pathogenic/Likely pathogenic ★★ same residue
- COL2A1 p.Cys1323Trp Pathogenic/Likely pathogenic ★★ same residue
- COL2A1 p.Cys1323Ser Pathogenic ★ same residue
- COL2A1 p.Cys1323fs 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-cys1323 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown