SEMA3B p.Ser596=
c.1788G>A · VCV3356585
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00891%, eas)
Conditions
1
SEMA3B-related disorder
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 -2 | GERP -3.6 |
| Overall | ||
| CADD | 9.27 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00891%
East Asian · 4/44,872 alleles
Filtering AF
0.00298%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0018%
Overall
0.000372%
6/1,612,116 alleles · very rare
exomes 5/1,459,984 · genomes 1/152,132 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00891% | 11,218 |
| European (non-Finnish) | 0.00017% | 589,887 |
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
- SEMA3B
- Protein
- p.Ser596=
- Coding
- c.1788G>A
- MANE Select
- NM_001290060
- Type
- single nucleotide variant
- Location
- chr3:50275787 (GRCh38)
- Gene constraint
- LOEUF 1.219 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.84
- Residue 596
- the ig-like c2-type domain
Disease context
SEMA3B-related disorder
Similar variants
- SEMA3B p.Ala680Val Likely benign ★★ same condition
- SEMA3B p.Arg148Trp Uncertain significance ★ ⚠ same condition
- SEMA3B p.Arg371Cys Uncertain significance ★ ⚠ same condition
- SEMA3B p.Arg418Ser Uncertain significance ★ ⚠ same condition
- SEMA3B p.Arg728Gly Uncertain significance ★ ⚠ same condition
- SEMA3B p.Asn221Lys Uncertain significance ★ ⚠ same condition
- SEMA3B p.Gly568= Uncertain significance ★ same condition
- SEMA3B p.Gly650Asp 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/sema3b-p-ser596 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown