SH3BP2 p.Pro189=
c.567G>A · rs1416781918 · VCV2093190
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00682%, eas)
Conditions
1
cherubism
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 -20 | GERP -2.9 |
| Overall | ||
| CADD | 0.137 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00682%
East Asian · 3/44,020 alleles
Filtering AF
0.00181%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000901%
Overall
0.000941%
15/1,594,746 alleles · very rare
exomes 12/1,442,522 · genomes 3/152,224 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00682% | 14,673 |
| African / African-American | 0.00402% | 24,883 |
| Finnishnot grpmax-eligible | 0.0032% | 31,247 |
| European (non-Finnish) | 0.000598% | 167,198 |
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
- SH3BP2
- Protein
- p.Pro189=
- Coding
- c.567G>A
- MANE Select
- NM_001122681
- dbSNP
- rs1416781918
- Type
- single nucleotide variant
- Location
- chr4:2827655 (GRCh38)
- Gene constraint
- LOEUF 0.958 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 66.04 · 2 PDB
- Residue 189
- the 'disordered' region
Similar variants
- SH3BP2 p.Pro189Leu Uncertain significance ★★ ⚠ same residue
- SH3BP2 p.Pro189Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
- SH3BP2 p.Arg415Gln Pathogenic ★★ ⚠ same condition
- SH3BP2 p.Gly420Arg Pathogenic ★★ ⚠ same condition
- SH3BP2 p.Pro418Arg Pathogenic ★★ ⚠ same condition
- SH3BP2 p.Pro418His Pathogenic/Likely pathogenic ★★ ⚠ same condition
- SH3BP2 p.Pro418Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
- SH3BP2 p.Pro418Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
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/sh3bp2-p-pro189 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown