SH3BP2 p.Pro69=
c.207G>A · rs1017260878 · VCV766557
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0117%, 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 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -12 | GERP -2.2 |
| Overall | ||
| CADD | 1.24 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0117%
Admixed American · 7/59,992 alleles
Filtering AF
0.00543%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00381%
Overall
0.000744%
12/1,613,840 alleles · ultra-rare
exomes 8/1,461,684 · genomes 4/152,156 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0117% | 8,570 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,478 |
| African / African-American | 0.00134% | 74,906 |
| South Asian | 0.0011% | 91,060 |
| European (non-Finnish) | 0.00017% | 589,957 |
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.Pro69=
- Coding
- c.207G>A
- MANE Select
- NM_001122681
- dbSNP
- rs1017260878
- Type
- single nucleotide variant
- Location
- chr4:2823005 (GRCh38)
- Gene constraint
- LOEUF 0.958 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 66.04 · 2 PDB
- Residue 69
- the ph domain
Similar variants
- SH3BP2 p.Pro69Ser Uncertain significance ★★ ⚠ same residue
- SH3BP2 p.Pro69Leu 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-pro69 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown