COL11A1 p.Pro496=
c.1488G>A · rs772310071 · VCV392656
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00196%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.66 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.50 | loss · gain 0.20 · SpliceAI calls gain · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.39 | GERP -0.042, phastCons 0.99 |
| Overall | ||
| CADD | 24.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00196%
European (non-Finnish) · 23/1,172,180 alleles
Filtering AF
0.00131%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00109%
Overall
0.00156%
25/1,601,790 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00196% | 50,964 |
| Remaining individualsnot grpmax-eligible | 0.00162% | 61,874 |
| South Asian | 0.00111% | 89,812 |
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
- COL11A1
- Protein
- p.Pro496=
- Coding
- c.1488G>A
- MANE Select
- NM_001854
- dbSNP
- rs772310071
- Type
- single nucleotide variant
- Location
- chr1:103015668 (GRCh38)
- Gene constraint
- LOEUF 0.349 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 53.06
- Residue 496
- the 'triple-helical region (interrupted)' region; the 'disordered' region
Similar variants
- COL11A1 p.Pro496Leu Uncertain significance ★★ ⚠ same residue
- COL11A1 p.Pro496Thr Uncertain significance ★ ⚠ same residue
- COL11A1 c.1245+1G>A Pathogenic/Likely pathogenic ★★ same type
- COL11A1 c.1245+1G>T Pathogenic/Likely pathogenic ★★ same type
- COL11A1 c.1629+1G>A Likely pathogenic ★★ same type
- COL11A1 c.1630-1G>T Pathogenic ★★ same type
- COL11A1 c.1791+1G>T Likely pathogenic ★★ same type
- COL11A1 c.1900-1G>A Likely 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/col11a1-p-pro496 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown