SH3BP2 p.Pro231=
c.693C>T · rs748570052 · VCV2154800
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0198%, sas)
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 -4 | GERP -2.9 |
| Overall | ||
| CADD | 1.552 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0198%
South Asian · 18/91,050 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0106%
Overall
0.00205%
33/1,612,088 alleles · ultra-rare
exomes 31/1,460,042 · genomes 2/152,046 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0198% | 5,058 |
| East Asian | 0.00446% | 22,442 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,576 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,219 |
| African / African-American | 0.00267% | 37,422 |
| European (non-Finnish) | 0.000678% | 147,386 |
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.Pro231=
- Coding
- c.693C>T
- MANE Select
- NM_001122681
- dbSNP
- rs748570052
- Type
- single nucleotide variant
- Location
- chr4:2829599 (GRCh38)
- Gene constraint
- LOEUF 0.958 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 66.04 · 2 PDB
- Residue 231
- the 'disordered' region
Similar variants
- SH3BP2 p.Pro231Leu Uncertain significance ★ ⚠ same residue
- SH3BP2 p.Pro231Ser 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
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-pro231 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown