Is STUB1 p.Ser216fs (c.646dup) pathogenic?

STUB1 p.Ser216fs (c.646dup) is classified Pathogenic/Likely pathogenic in STUB1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-03-01). Ultra-rare (gnomAD MAF 7.265e-07); Associated with autosomal recessive spinocerebellar ataxia 16.

What condition is associated with STUB1 p.Ser216fs (c.646dup)?

STUB1 p.Ser216fs (c.646dup) is associated with autosomal recessive spinocerebellar ataxia 16, spinocerebellar ataxia 48 (ClinVar).

How common is STUB1 p.Ser216fs (c.646dup) in the general population?

STUB1 p.Ser216fs (c.646dup) is ultra-rare (gnomAD MAF 7.265e-07) (gnomAD).

STUB1 p.Ser216fs

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.646dup · rs1555475283 · VCV436887

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 7.265e-07)

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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.9	GERP 2.2, phastCons 1

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

Population frequency

dbSNP / gnomAD

Global frequency 7.26e-05% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: STUB1
Protein: p.Ser216fs
Coding: c.646dup
MANE Select: NM_001005920 · reported on NM_005861
dbSNP: rs1555475283
Type: Duplication
Location: chr16:682047 (GRCh38)

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

Also linked: spinocerebellar ataxia 48

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

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

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-ser216fs (accessed [today's date]).

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