SEMA3A p.Val45=
c.135G>C · rs139207450 · VCV726769
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.01%, afr)
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 0.9 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 8.36 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.01%
African / African-American · 758/74,964 alleles
Filtering AF
0.951%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.928%
Overall
0.0512%
826/1,612,962 alleles · low-frequency
exomes 404/1,460,730 · genomes 422/152,232 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.01% | 99 |
| Remaining individualsnot grpmax-eligible | 0.0544% | 1,837 |
| Admixed American | 0.0485% | 2,060 |
| Middle Eastern | 0.0165% | 6,056 |
| South Asian | 0.0011% | 90,744 |
| European (non-Finnish) | 0.000254% | 393,227 |
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
- SEMA3A
- Protein
- p.Val45=
- Coding
- c.135G>C
- MANE Select
- NM_006080
- dbSNP
- rs139207450
- Type
- single nucleotide variant
- Location
- chr7:84134929 (GRCh38)
- Gene constraint
- LOEUF 0.453 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 84.50
- Residue 45
- the sema domain
Similar variants
- SEMA3A p.Ala491Thr Uncertain significance ★★ ⚠ same type
- SEMA3A p.Ala523Val Uncertain significance ★★ ⚠ same type
- SEMA3A p.Arg419His Uncertain significance ★★ ⚠ same type
- SEMA3A p.Arg516Trp Uncertain significance ★★ ⚠ same type
- SEMA3A p.Arg617Ter Uncertain significance ★★ same type
- SEMA3A p.Arg637His Uncertain significance ★★ ⚠ same type
- SEMA3A p.Arg66Trp Uncertain significance ★★ ⚠ same type
- SEMA3A p.Arg733Cys 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/sema3a-p-val45 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown