SEPTIN9 p.Ala559=
c.1677G>A · rs756067727 · VCV1682679
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0169%, mid)
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 -5.8 | GERP -4.3 |
| Overall | ||
| CADD | 7.655 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0169%
Middle Eastern · 1/5,920 alleles
Filtering AF
0.000751%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000281%
Overall
0.00075%
12/1,600,734 alleles · ultra-rare
exomes 12/1,452,234 · genomes 0/148,500 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0169% | 5,920 |
| East Asian | 0.00453% | 22,073 |
| European (non-Finnish) | 0.000766% | 130,630 |
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
- SEPTIN9
- Protein
- p.Ala559=
- Coding
- c.1677G>A
- MANE Select
- NM_001113491
- dbSNP
- rs756067727
- Type
- single nucleotide variant
- Location
- chr17:77498574 (GRCh38)
- Gene constraint
- LOEUF 0.39 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 67.42 · 3 PDB
- Residue 559
- the septin-type g domain; an α-helix
Similar variants
- SEPTIN9 p.Arg106Trp Pathogenic ★★ same type
- SEPTIN9 c.1380+5G>C Uncertain significance ★★ same type
- SEPTIN9 p.Ala183Val Uncertain significance ★★ ⚠ same type
- SEPTIN9 p.Ala201Thr Uncertain significance ★★ ⚠ same type
- SEPTIN9 p.Ala234Val Uncertain significance ★★ ⚠ same type
- SEPTIN9 p.Ala266Thr Uncertain significance ★★ ⚠ same type
- SEPTIN9 p.Ala571Thr Uncertain significance ★★ ⚠ same type
- SEPTIN9 p.Ala75Ser 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/septin9-p-ala559 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown