SH3PXD2B p.Pro366=
c.1098G>A · rs768050049 · VCV3022319
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.039 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -7.5 | GERP -4.9 |
| Overall | ||
| CADD | 7.598 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,062 alleles
Filtering AF
0.00298%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0018%
Overall
0.00192%
31/1,614,008 alleles · ultra-rare
exomes 29/1,461,756 · genomes 2/152,252 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,062 |
| East Asian | 0.00891% | 11,218 |
| European (non-Finnish) | 0.0022% | 45,384 |
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
- SH3PXD2B
- Protein
- p.Pro366=
- Coding
- c.1098G>A
- MANE Select
- NM_001017995
- dbSNP
- rs768050049
- Type
- single nucleotide variant
- Location
- chr5:172346226 (GRCh38)
- Gene constraint
- LOEUF 0.655 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 56.95
- Residue 366
- the 'disordered' region
Similar variants
- SH3PXD2B p.Pro366Leu Uncertain significance ★ same residue
- SH3PXD2B p.Arg43Trp Likely pathogenic ★★ same type
- SH3PXD2B c.*1199T>C Uncertain significance ★★ same type
- SH3PXD2B p.Ala309Val Uncertain significance ★★ ⚠ same type
- SH3PXD2B p.Ala431Thr Uncertain significance ★★ ⚠ same type
- SH3PXD2B p.Ala431Val Uncertain significance ★★ ⚠ same type
- SH3PXD2B p.Ala498Thr Uncertain significance ★★ ⚠ same type
- SH3PXD2B p.Ala857Ser Uncertain significance ★★ ⚠ same type
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/sh3pxd2b-p-pro366 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown