SEPTIN9 p.Phe366=
c.1098C>T · rs199574222 · VCV728457
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, 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 -10 | GERP -5.4 |
| Overall | ||
| CADD | 7.407 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00186%
30/1,613,542 alleles · ultra-rare
exomes 28/1,461,394 · genomes 2/152,148 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| Admixed American | 0.005% | 20,003 |
| African / African-American | 0.004% | 24,971 |
| European (non-Finnish) | 0.00186% | 53,628 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,454 |
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.Phe366=
- Coding
- c.1098C>T
- MANE Select
- NM_001113491
- dbSNP
- rs199574222
- Type
- single nucleotide variant
- Location
- chr17:77488295 (GRCh38)
- Gene constraint
- LOEUF 0.39 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 67.42 · 3 PDB
- Residue 366
- the septin-type g domain
Similar variants
- SEPTIN9 p.Phe366Ser Uncertain significance ★ ⚠ same residue
- 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
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-phe366 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown