SH3BP2 p.Val352=
c.1056G>A · rs1257654174 · VCV1143815
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
Conditions
1
cherubism
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>T here scores Δ0.34 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.1 | GERP -1.1, phastCons 1 |
| Overall | ||
| CADD | 8.302 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/60,020 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000372%
6/1,613,356 alleles · very rare
exomes 6/1,461,172 · genomes 0/152,184 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 30,010 |
| East Asian | 0.00223% | 44,860 |
| Finnishnot grpmax-eligible | 0.00158% | 63,352 |
| European (non-Finnish) | 0.000169% | 589,981 |
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.Val352=
- Coding
- c.1056G>A
- MANE Select
- NM_001122681
- dbSNP
- rs1257654174
- Type
- single nucleotide variant
- Location
- chr4:2829962 (GRCh38)
- Gene constraint
- LOEUF 0.958 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 66.04 · 2 PDB
- Residue 352
- the 'disordered' region
Similar variants
- 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
- SH3BP2 p.Ala354Val 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-val352 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown