COL2A1 p.Leu93=
c.279C>T · rs774746221 · VCV748517
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00668%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.24 | donor loss, 16 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.2 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 13.81 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
East Asian · 3/44,902 alleles
Filtering AF
0.00226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00135%
Overall
0.000806%
13/1,613,848 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00668% | 14,967 |
| Admixed American | 0.00667% | 15,002 |
| Finnishnot grpmax-eligible | 0.00312% | 32,012 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,478 |
| African / African-American | 0.00133% | 74,924 |
| European (non-Finnish) | 0.00017% | 589,922 |
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.Leu93=
- Coding
- c.279C>T
- MANE Select
- NM_001844
- dbSNP
- rs774746221
- Type
- single nucleotide variant
- Location
- chr12:47999932 (GRCh38)
- Gene constraint
- LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 53.56 · 11 PDB
- Residue 93
- a turn
Similar variants
- COL2A1 p.Leu93Arg 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-leu93 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown