Is SEPTIN9 p.Pro173= (c.519C>T) pathogenic?

SEPTIN9 p.Pro173= (c.519C>T) is classified Conflicting classifications of pathogenicity in SEPTIN9 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-07-02). Ultra-rare (popmax 0.0136%, eas); Associated with amyotrophic neuralgia.

What condition is associated with SEPTIN9 p.Pro173= (c.519C>T)?

SEPTIN9 p.Pro173= (c.519C>T) is associated with amyotrophic neuralgia (ClinVar).

How common is SEPTIN9 p.Pro173= (c.519C>T) in the general population?

SEPTIN9 p.Pro173= (c.519C>T) is ultra-rare (popmax 0.0136%, eas) (gnomAD).

SEPTIN9 p.Pro173=

c.519C>T · rs763954299 · VCV325545

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0136%, eas)

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 -7.3	GERP -3.6
Overall
CADD	3.105	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0136% East Asian · 6/44,256 alleles

Filtering AF 0.00585% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00398%

Overall 0.002% 32/1,603,394 alleles · ultra-rare exomes 29/1,451,242 · genomes 3/152,152 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0136%	7,376
Remaining individualsnot grpmax-eligible	0.00483%	20,683
African / African-American	0.00402%	24,881
Ashkenazi Jewishnot grpmax-eligible	0.00341%	29,362
Admixed American	0.00171%	58,436
European (non-Finnish)	0.00145%	69,155
South Asian	0.00112%	89,552

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.Pro173=
Coding: c.519C>T
MANE Select: NM_001113491
dbSNP: rs763954299
Type: single nucleotide variant
Location: chr17:77402501 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.42 · 3 PDB
Residue 173: the 'disordered' region

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.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
SEPTIN9 c.1043-4G>A Benign/Likely 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-pro173 (accessed [today's date]).

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