SH3BP2 p.Pro289=
c.867C>T · rs151102529 · VCV1099126
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 -3.9 | GERP -3.2 |
| Overall | ||
| CADD | 5.795 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00528%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00447%
Overall
0.00546%
88/1,613,032 alleles · ultra-rare
exomes 78/1,460,860 · genomes 10/152,172 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| African / African-American | 0.0107% | 9,363 |
| East Asian | 0.00668% | 14,963 |
| European (non-Finnish) | 0.00602% | 16,619 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,236 |
| South Asian | 0.0022% | 45,542 |
| Finnishnot grpmax-eligible | 0.00158% | 63,122 |
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.Pro289=
- Coding
- c.867C>T
- MANE Select
- NM_001122681
- dbSNP
- rs151102529
- Type
- single nucleotide variant
- Location
- chr4:2829773 (GRCh38)
- Gene constraint
- LOEUF 0.958 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 66.04 · 2 PDB
- Residue 289
- the 'disordered' region
Similar variants
- SH3BP2 p.Pro289His Uncertain significance ★ ⚠ 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
- SH3BP2 p.Ala155Thr Uncertain significance ★★ ⚠ 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-pro289 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown