SEMA4A p.Pro27=
c.81G>A · rs777184442 · VCV3051241
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00896%, sas)
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 -3.9 | GERP -3.5 |
| Overall | ||
| CADD | 4.042 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00896%
South Asian · 8/89,322 alleles
Filtering AF
0.00444%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00317%
Overall
0.00168%
27/1,604,920 alleles · very rare
exomes 24/1,452,662 · genomes 3/152,258 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00896% | 11,165 |
| Admixed American | 0.00686% | 14,569 |
| East Asian | 0.00448% | 22,335 |
| African / African-American | 0.00134% | 74,902 |
| European (non-Finnish) | 0.00102% | 98,030 |
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.Pro27=
- Coding
- c.81G>A
- MANE Select
- NM_022367
- dbSNP
- rs777184442
- Type
- single nucleotide variant
- Location
- chr1:156154659 (GRCh38)
- Gene constraint
- LOEUF 0.858 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.05
Similar variants
- SEMA4A p.Pro27Arg Uncertain significance ★ ⚠ same residue
- SEMA4A p.Pro27Leu Uncertain significance ★ ⚠ same residue
- SEMA4A p.Pro27Ser Uncertain significance ★ ⚠ same residue
- SEMA4A p.Pro27dup 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
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-pro27 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown