Is STUB1 p.Arg40fs (c.116dup) pathogenic?

STUB1 p.Arg40fs (c.116dup) is classified Uncertain significance in STUB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-22). Associated with autosomal recessive spinocerebellar ataxia 16.

What condition is associated with STUB1 p.Arg40fs (c.116dup)?

STUB1 p.Arg40fs (c.116dup) is associated with autosomal recessive spinocerebellar ataxia 16 (ClinVar).

STUB1 p.Arg40fs

Q: How is Autosomal recessive cerebellar ataxia due to STUB1 deficiency inherited?

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

c.116dup · VCV3731353

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

autosomal recessive spinocerebellar ataxia 16

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1

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

Variant & gene context

Gene: STUB1
Protein: p.Arg40fs
Coding: c.116dup
MANE Select: NM_005861
Type: Duplication
Location: chr16:680638 (GRCh38)
Gene constraint: LOEUF 1.294 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.84 · 27 PDB

Full STUB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive spinocerebellar ataxia 16 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive cerebellar ataxia due to STUB1 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

Similar variants

STUB1 p.Asn65Ser Pathogenic/Likely pathogenic ★★ same condition
STUB1 p.Val264fs Pathogenic/Likely pathogenic ★★ same condition
STUB1 p.Arg173Leu Uncertain significance ★★ ⚠ same condition
STUB1 p.Asn34Ser Uncertain significance ★★ ⚠ same condition
STUB1 p.Cys48Tyr Uncertain significance ★★ ⚠ same condition
STUB1 p.Gly249Val Uncertain significance ★★ ⚠ same condition
STUB1 p.Ile290Thr Uncertain significance ★★ ⚠ same condition
STUB1 p.Leu214= 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/stub1-p-arg40fs (accessed [today's date]).

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