Is SETX p.Val1674fs (c.5019del) pathogenic?

SETX p.Val1674fs (c.5019del) is classified Pathogenic in SETX (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-20). No gnomAD frequency available for this variant; Associated with amyotrophic lateral sclerosis type 4.

What condition is associated with SETX p.Val1674fs (c.5019del)?

SETX p.Val1674fs (c.5019del) is associated with amyotrophic lateral sclerosis type 4, spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 (ClinVar).

How common is SETX p.Val1674fs (c.5019del) in the general population?

SETX p.Val1674fs (c.5019del) is no gnomAD frequency available for this variant (gnomAD).

How is Amyotrophic lateral sclerosis type 4 inherited?

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

SETX p.Val1674fs

c.5019del · rs2539088969 · VCV2937674

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

amyotrophic lateral sclerosis type 4

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 0.87	GERP -0.43

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SETX
Protein: p.Val1674fs
Coding: c.5019del
MANE Select: NM_015046
dbSNP: rs2539088969
Type: Deletion
Location: chr9:132326579 (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

amyotrophic lateral sclerosis type 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2

For Amyotrophic lateral sclerosis type 4 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Childhood

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-val1674fs (accessed [today's date]).

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