Is SEPTIN9 p.Ser482= (c.1446G>A) pathogenic?

SEPTIN9 p.Ser482= (c.1446G>A) is classified Benign/Likely benign in SEPTIN9 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-08). Rare (popmax 0.577%, mid); Associated with amyotrophic neuralgia.

What condition is associated with SEPTIN9 p.Ser482= (c.1446G>A)?

SEPTIN9 p.Ser482= (c.1446G>A) is associated with amyotrophic neuralgia (ClinVar).

How common is SEPTIN9 p.Ser482= (c.1446G>A) in the general population?

SEPTIN9 p.Ser482= (c.1446G>A) is rare (popmax 0.577%, mid) (gnomAD).

SEPTIN9 p.Ser482=

c.1446G>A · rs80015943 · VCV325562

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.577%, mid)

Conditions

amyotrophic neuralgia

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 -8	GERP -5.4
Overall
CADD	0.14	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.577% Middle Eastern · 35/6,062 alleles

Filtering AF 0.427% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.375%

Overall 0.0287% 463/1,614,128 alleles · rare exomes 407/1,461,820 · genomes 56/152,308 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.577%	173
East Asian	0.412%	243
Ashkenazi Jewishnot grpmax-eligible	0.0912%	1,097
Remaining individualsnot grpmax-eligible	0.0528%	1,894
South Asian	0.0231%	4,337
European (non-Finnish)	0.0127%	7,867
Admixed American	0.0117%	8,576
African / African-American	0.00666%	15,007

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.Ser482=
Coding: c.1446G>A
MANE Select: NM_001113491
dbSNP: rs80015943
Type: single nucleotide variant
Location: chr17:77492686 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.42 · 3 PDB
Residue 482: the septin-type g domain; an α-helix

Full SEPTIN9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

amyotrophic neuralgia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SEPTIN9 p.Ser482Leu Uncertain significance ★ ⚠ same residue
SEPTIN9 p.Arg106Trp Pathogenic ★★ same condition
SEPTIN9 p.Arg268Trp Uncertain significance ★★ ⚠ same condition
SEPTIN9 p.Arg407Cys Uncertain significance ★★ ⚠ same condition
SEPTIN9 p.Arg45Gln Uncertain significance ★★ ⚠ same condition
SEPTIN9 p.Glu489Lys Uncertain significance ★★ ⚠ same condition
SEPTIN9 p.Val68Met Uncertain significance ★★ ⚠ same condition
SEPTIN9 c.1042+10C>T Benign ★★ same condition

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-ser482 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown