COL22A1 p.Pro72=
c.216C>T · rs139880147 · VCV2658853
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 -7.3 | GERP -4.4 |
| Overall | ||
| CADD | 5.708 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,048 alleles
Filtering AF
0.00815%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00633%
Overall
0.00175%
28/1,600,832 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,048 |
| African / African-American | 0.0147% | 6,811 |
| Remaining individualsnot grpmax-eligible | 0.00968% | 10,331 |
| East Asian | 0.00226% | 44,336 |
| European (non-Finnish) | 0.000766% | 130,503 |
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.Pro72=
- Coding
- c.216C>T
- MANE Select
- NM_152888
- dbSNP
- rs139880147
- Type
- single nucleotide variant
- Location
- chr8:138878192 (GRCh38)
- Gene constraint
- LOEUF 1.005 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 54.25
- Residue 72
- the vwfa 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-pro72 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown