SH3D19 p.Ser95=
c.285G>A · VCV4873243
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.031%, mid)
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 · C>A here scores Δ0.39 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.2 | GERP -4.9 |
| Overall | ||
| CADD | 4.072 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.031%
Middle Eastern · 1/3,230 alleles
Filtering AF
0.0136%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0128%
Overall
0.0136%
168/1,232,122 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.031% | 3,230 |
| South Asian | 0.0247% | 4,054 |
| European (non-Finnish) | 0.0157% | 6,374 |
| African / African-American | 0.00621% | 16,109 |
| Remaining individualsnot grpmax-eligible | 0.00437% | 22,883 |
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
- SH3D19
- Protein
- p.Ser95=
- Coding
- c.285G>A
- MANE Select
- NM_001378122
- Type
- single nucleotide variant
- Location
- chr4:151176907 (GRCh38)
- Gene constraint
- LOEUF 0.629 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.09
- Residue 95
- the 'disordered' region
Similar variants
- EBP p.Ala95Thr Uncertain significance ★★ ⚠ same residue
- EBP p.Arg110Gln Pathogenic/Likely pathogenic ★★ same type
- EBP p.Arg110Ter Pathogenic ★★ same type
- EBP p.Arg147Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
- EBP p.Arg147His Pathogenic ★★ ⚠ same type
- EBP p.Arg62Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
- EBP p.Glu80Lys Pathogenic/Likely pathogenic ★★ same type
- EBP p.Gly161Arg Likely pathogenic ★★ 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/sh3d19-p-ser95 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown