SEMA3A p.Pro486=
c.1458G>A · rs77413754 · VCV778023
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.69%, 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 0.5 | GERP -0.98, phastCons 1 |
| Overall | ||
| CADD | 11.32 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.69%
African / African-American · 2,011/74,698 alleles
Filtering AF
2.59%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.55%
Overall
0.519%
8,344/1,607,712 alleles · low-frequency
exomes 6,813/1,458,028 · genomes 1,531/149,684 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.69% | 37 |
| Remaining individualsnot grpmax-eligible | 0.599% | 167 |
| European (non-Finnish) | 0.485% | 206 |
| Admixed American | 0.26% | 384 |
| Middle Eastern | 0.0826% | 1,210 |
| South Asian | 0.0728% | 1,374 |
| Finnishnot grpmax-eligible | 0.0377% | 2,653 |
| East Asian | 0.00447% | 22,370 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00339% | 29,500 |
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.Pro486=
- Coding
- c.1458G>A
- MANE Select
- NM_006080
- dbSNP
- rs77413754
- Type
- single nucleotide variant
- Location
- chr7:83985472 (GRCh38)
- Gene constraint
- LOEUF 0.453 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 84.50
- Residue 486
- the sema domain
Similar variants
- SEMA3A p.Pro486Gln Uncertain significance ★ ⚠ same residue
- SEMA3A p.Pro486Leu Uncertain significance ★ ⚠ same residue
- 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
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-pro486 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown