SEMA4A p.Pro296=
c.888G>C · rs141021787 · VCV1092482
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0949%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -16 | GERP -5 |
| Overall | ||
| CADD | 0.14 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0949%
African / African-American · 71/74,846 alleles
Filtering AF
0.0771%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0706%
Overall
0.00528%
85/1,609,992 alleles · ultra-rare
exomes 40/1,457,962 · genomes 45/152,030 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0949% | 1,054 |
| Remaining individualsnot grpmax-eligible | 0.00965% | 10,365 |
| Admixed American | 0.00334% | 29,924 |
| European (non-Finnish) | 0.00051% | 196,232 |
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.Pro296=
- Coding
- c.888G>C
- MANE Select
- NM_022367
- dbSNP
- rs141021787
- Type
- single nucleotide variant
- Location
- chr1:156161423 (GRCh38)
- Gene constraint
- LOEUF 0.858 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.05
- Residue 296
- the sema domain
Similar variants
- 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
- SEMA4A p.Ala585Ser 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-pro296 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown