COL22A1 p.Asp755=
c.2265C>T · VCV3495351
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0739%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>C here scores Δ0.22 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.1 | GERP -3.5 |
| Overall | ||
| CADD | 0.183 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0739%
African / African-American · 55/74,438 alleles
Filtering AF
0.0582%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0526%
Overall
0.00657%
104/1,583,286 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0739% | 1,353 |
| South Asian | 0.0382% | 2,620 |
| Admixed American | 0.0107% | 9,351 |
| Remaining individualsnot grpmax-eligible | 0.0098% | 10,205 |
| European (non-Finnish) | 0.000344% | 290,739 |
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
- COL22A1
- Protein
- p.Asp755=
- Coding
- c.2265C>T
- MANE Select
- NM_152888
- Type
- single nucleotide variant
- Location
- chr8:138722072 (GRCh38)
- Gene constraint
- LOEUF 1.005 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 54.25
- Residue 755
- the 'disordered' region; the collagen-like 5 domain
Similar variants
- COL22A1 p.Glu736Asp Benign ★★ same type
- COL22A1 p.Gly1180= Benign ★★ same type
- COL22A1 p.Pro763Leu Benign ★★ same type
- COL22A1 p.Ala1005Ser Uncertain significance ★ ⚠ same type
- COL22A1 p.Ala103Val Uncertain significance ★ ⚠ same type
- COL22A1 p.Ala1077Gly Uncertain significance ★ ⚠ same type
- COL22A1 p.Ala120Ser Uncertain significance ★ ⚠ same type
- COL22A1 p.Ala1212Ser 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/col22a1-p-asp755 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown