SEPTIN9 p.Pro404=
c.1212G>A · rs748775517 · VCV2445514
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0133%, amr)
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 -20 | GERP -5.4 |
| Overall | ||
| CADD | 1.521 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0133%
Admixed American · 8/59,990 alleles
Filtering AF
0.00662%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00483%
Overall
0.00124%
20/1,613,596 alleles · ultra-rare
exomes 19/1,461,466 · genomes 1/152,130 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0133% | 7,499 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,462 |
| South Asian | 0.0011% | 91,086 |
| European (non-Finnish) | 0.000848% | 117,986 |
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.Pro404=
- Coding
- c.1212G>A
- MANE Select
- NM_001113491
- dbSNP
- rs748775517
- Type
- single nucleotide variant
- Location
- chr17:77488814 (GRCh38)
- Gene constraint
- LOEUF 0.39 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 67.42 · 3 PDB
- Residue 404
- the septin-type g domain; an α-helix
Similar variants
- SEPTIN9 p.Pro404Leu 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-pro404 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown