COL11A2 p.Ala407=
c.1221G>A · rs1554221935 · VCV508701
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 0.00133%, 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 |
|---|---|---|
| Pangolin | Δ0.20 | loss · gain 0.01 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP -1.8, phastCons 1 |
| Overall | ||
| CADD | 22.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/74,950 alleles
Filtering AF
7.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.000342%
5/1,461,676 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00133% | 74,950 |
| European (non-Finnish) | 0.000339% | 294,969 |
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
- COL11A2
- Protein
- p.Ala407=
- Coding
- c.1221G>A
- MANE Select
- NM_080680
- dbSNP
- rs1554221935
- Type
- single nucleotide variant
- Location
- chr6:33180964 (GRCh38)
- Gene constraint
- LOEUF 0.503 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 50.18
- Residue 407
- the 'nonhelical region' region; the 'disordered' region; the collagen-like 1 domain
Similar variants
- COL11A2 p.Ala407Val Uncertain significance ★★ ⚠ same residue
- COL11A2 p.Ala407Glu Uncertain significance ★ ⚠ same residue
- COL11A2 p.Ala407fs Likely pathogenic ★ same residue
- COL11A2 c.1119+1G>A Likely pathogenic ★★ same type
- COL11A2 c.1819-2A>G Likely pathogenic ★★ same type
- COL11A2 c.3852+1G>T Likely pathogenic ★★ same type
- COL11A2 c.4392+1G>A Pathogenic ★★ same type
- COL11A2 c.607-2A>T 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/col11a2-p-ala407 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown