SEMA3B p.Pro375=
c.1125G>A · rs61737738 · VCV775873
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 12.4%, afr) — too common for a highly-penetrant pathogenic allele
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 -1.5 | GERP -3.9 |
| Overall | ||
| CADD | 7.604 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
12.4%
African / African-American · 9,319/74,984 alleles
Filtering AF
12.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 12.1%
Overall
0.645%
10,405/1,613,282 alleles · common
exomes 5,165/1,460,964 · genomes 5,240/152,318 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 12.4% | 8 |
| Remaining individualsnot grpmax-eligible | 0.818% | 122 |
| Admixed American | 0.702% | 142 |
| Middle Eastern | 0.233% | 429 |
| South Asian | 0.0538% | 1,858 |
| European (non-Finnish) | 0.0078% | 12,823 |
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.Pro375=
- Coding
- c.1125G>A
- MANE Select
- NM_001290060
- dbSNP
- rs61737738
- Type
- single nucleotide variant
- Location
- chr3:50274045 (GRCh38)
- Gene constraint
- LOEUF 1.219 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.84
- Residue 375
- the sema domain
Similar variants
- SEMA3B p.Ala680Val Likely benign ★★ same type
- SEMA3B p.Ala325Gly Uncertain significance ★ ⚠ same type
- SEMA3B p.Ala426Gly Uncertain significance ★ ⚠ same type
- SEMA3B p.Ala4Asp Uncertain significance ★ ⚠ same type
- SEMA3B p.Ala674Val Uncertain significance ★ ⚠ same type
- SEMA3B p.Ala6Thr Uncertain significance ★ ⚠ same type
- SEMA3B p.Arg148Trp Uncertain significance ★ ⚠ same type
- SEMA3B p.Arg160Thr 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/sema3b-p-pro375 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown