COL9A2 p.Pro462=
c.1386G>A · rs780301075 · VCV2003255
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00173%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.015 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -13 | GERP -3 |
| Overall | ||
| CADD | 0.183 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00173%
European (non-Finnish) · 20/1,154,222 alleles
Filtering AF
0.00113%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00092%
Overall
0.00128%
20/1,561,388 alleles · very rare
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
- COL9A2
- Protein
- p.Pro462=
- Coding
- c.1386G>A
- MANE Select
- NM_001852
- dbSNP
- rs780301075
- Type
- single nucleotide variant
- Location
- chr1:40303822 (GRCh38)
- Gene constraint
- LOEUF 0.817 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 54.99 · 4 PDB
- Residue 462
- the 'disordered' region; a UniProt-annotated variant site (sequence variant); the 'triple-helical region 3 (col3)' region
Similar variants
- COL9A2 p.Pro462Leu Uncertain significance ★★ ⚠ same residue
- COL9A2 p.Pro462Arg Uncertain significance ★ ⚠ same residue
- COL9A2 c.186+1G>A Pathogenic/Likely pathogenic ★★ same type
- COL9A2 p.Arg136Ter Pathogenic/Likely pathogenic ★★ same type
- COL9A2 p.Arg504Ter Pathogenic/Likely pathogenic ★★ same type
- COL9A2 c.1107+4A>G Uncertain significance ★★ same type
- COL9A2 c.1792+5G>A Uncertain significance ★★ same type
- COL9A2 c.1793-9T>A Uncertain significance ★★ 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/col9a2-p-pro462 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown