Is SETX p.Ser530fs (c.1589_1590del) pathogenic?

SETX p.Ser530fs (c.15891590del) is classified Pathogenic in SETX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). Associated with spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2.

What condition is associated with SETX p.Ser530fs (c.1589_1590del)?

SETX p.Ser530fs (c.1589_1590del) is associated with spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 (ClinVar).

SETX p.Ser530fs

Q: How is Spinocerebellar ataxia with axonal neuropathy type 2 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1589_1590del · VCV4294099

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 10 of 26
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: SETX
Protein: p.Ser530fs
Coding: c.1589_1590del
MANE Select: NM_015046
Type: Microsatellite
Location: chr9:132330008 (GRCh38)
Gene constraint: LOEUF 0.442 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 52.93

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

Disease context

spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Spinocerebellar ataxia with axonal neuropathy type 2 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 1 000 000 (France)

Similar variants

SETX p.Ser530= Likely benign ★ same residue
SETX p.Glu1770fs Pathogenic/Likely pathogenic ★★ same condition
SETX p.His2243fs Pathogenic/Likely pathogenic ★★ same condition
SETX p.Val2374fs Pathogenic/Likely pathogenic ★★ same condition
SETX p.Ile1016del Uncertain significance ★★ same condition
SETX p.Ile741del Uncertain significance ★★ same condition
SETX p.Lys909del Uncertain significance ★★ same condition
SETX p.Pro1587del Uncertain significance ★★ 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/setx-p-ser530fs (accessed [today's date]).

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