COL2A1 p.Val46=
c.138G>A · VCV4776924
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00401%, afr)
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 -0.95 | GERP -3.8, phastCons 0.003 |
| Overall | ||
| CADD | 7.538 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00401%
African / African-American · 3/74,866 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000495%
Overall
0.000248%
4/1,613,774 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00401% | 24,955 |
| European (non-Finnish) | 8.47e-05% | 1,180,012 |
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.Val46=
- Coding
- c.138G>A
- MANE Select
- NM_001844
- Type
- single nucleotide variant
- Location
- chr12:48000073 (GRCh38)
- Gene constraint
- LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 53.56 · 11 PDB
- Residue 46
- a β-strand; the vwfc domain
Similar variants
- COL2A1 p.Val46Ala Uncertain significance ★ ⚠ 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-val46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown