Is SETX p.Pro1675fs (c.5024del) pathogenic?

SETX p.Pro1675fs (c.5024del) is classified Uncertain significance in SETX (ClinVar, Single submitter, 1 submitter; last evaluated 2017-12-03). Very rare (popmax 0.0011%, sas); Associated with spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2.

What condition is associated with SETX p.Pro1675fs (c.5024del)?

SETX p.Pro1675fs (c.5024del) is associated with spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 (ClinVar).

How common is SETX p.Pro1675fs (c.5024del) in the general population?

SETX p.Pro1675fs (c.5024del) is very rare (popmax 0.0011%, sas) (gnomAD).

SETX p.Pro1675fs

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.5024del · rs1554820021 · VCV522755

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 -9.5	GERP -3

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,086 alleles

Overall 6.19e-05% 1/1,614,218 alleles · very rare exomes 1/1,461,888 · genomes 0/152,330 · joint denominator

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: SETX
Protein: p.Pro1675fs
Coding: c.5024del
MANE Select: NM_015046
dbSNP: rs1554820021
Type: Deletion
Location: chr9:132326574 (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 c.6843-3_6843-1del Likely pathogenic ★★ same condition
SETX p.Asp2332fs Pathogenic/Likely pathogenic ★★ same condition
SETX p.Gln1864fs Pathogenic/Likely pathogenic ★★ same condition
SETX p.Lys796fs Pathogenic ★★ same condition
SETX p.Thr1755fs Pathogenic ★★ same condition
SETX p.Arg2529fs Uncertain significance ★★ same condition
SETX p.His476_Leu477del Uncertain significance ★★ same condition
SETX p.Ile664_Glu665del 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-pro1675fs (accessed [today's date]).

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