SEMA4A p.Phe145=
c.435C>T · rs767374593 · VCV1112032
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0107%, afr)
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 Δ0.25 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -7.5 | GERP -4.7 |
| Overall | ||
| CADD | 4.222 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0107%
African / African-American · 8/74,882 alleles
Filtering AF
0.00528%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00381%
Overall
0.00291%
47/1,613,704 alleles · ultra-rare
exomes 42/1,461,582 · genomes 5/152,122 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0107% | 9,360 |
| Admixed American | 0.005% | 20,000 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,825 |
| East Asian | 0.00446% | 22,442 |
| European (non-Finnish) | 0.00246% | 40,681 |
| South Asian | 0.0022% | 45,541 |
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
- SEMA4A
- Protein
- p.Phe145=
- Coding
- c.435C>T
- MANE Select
- NM_022367
- dbSNP
- rs767374593
- Type
- single nucleotide variant
- Location
- chr1:156158459 (GRCh38)
- Gene constraint
- LOEUF 0.858 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.05
- Residue 145
- the sema domain
Similar variants
- SEMA4A p.Phe145Leu Uncertain significance ★ ⚠ same residue
- SEMA4A c.*208A>G Uncertain significance ★★ same type
- SEMA4A p.Ala114Thr Uncertain significance ★★ ⚠ same type
- SEMA4A p.Ala181Thr Uncertain significance ★★ ⚠ same type
- SEMA4A p.Ala337Val Uncertain significance ★★ same type
- SEMA4A p.Ala446Val Uncertain significance ★★ ⚠ same type
- SEMA4A p.Ala509Gly Uncertain significance ★★ ⚠ same type
- SEMA4A p.Ala570Thr 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/sema4a-p-phe145 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown