SEMA4A p.Phe233=
c.699T>C · rs1015406149 · VCV2956954
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0022%, sas)
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 0.34 | GERP -0.94, phastCons 0.99 |
| Overall | ||
| CADD | 12.56 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0022%
South Asian · 2/91,054 alleles
Filtering AF
0.000365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000137%
Overall
0.00031%
5/1,613,182 alleles · very rare
exomes 3/1,461,600 · genomes 2/151,582 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0022% | 45,527 |
| European (non-Finnish) | 0.000254% | 393,255 |
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.Phe233=
- Coding
- c.699T>C
- MANE Select
- NM_022367
- dbSNP
- rs1015406149
- Type
- single nucleotide variant
- Location
- chr1:156160918 (GRCh38)
- Gene constraint
- LOEUF 0.858 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.05
- Residue 233
- 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-phe233 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown