Is UBAP1 p.Cys161fs (c.478_482dup) pathogenic?

UBAP1 p.Cys161fs (c.478482dup) is classified Likely pathogenic in UBAP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-06-01). Associated with spastic paraplegia 80, autosomal dominant.

What condition is associated with UBAP1 p.Cys161fs (c.478_482dup)?

UBAP1 p.Cys161fs (c.478_482dup) is associated with spastic paraplegia 80, autosomal dominant (ClinVar).

How is Autosomal dominant spastic paraplegia type 80 inherited?

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

UBAP1 p.Cys161fs

c.478_482dup · VCV3338070

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

spastic paraplegia 80, autosomal dominant

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 4 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.6	GERP -3.8

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

Variant & gene context

Gene: UBAP1
Protein: p.Cys161fs
Coding: c.478_482dup
MANE Select: NM_016525
Type: Duplication
Location: chr9:34241502 (GRCh38)
Gene constraint: LOEUF 0.285 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.60 · 3 PDB
Residue 161: a UniProt-annotated variant site (in spg80)

Full UBAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spastic paraplegia 80, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant spastic paraplegia type 80 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Childhood

Similar variants

UBAP1 p.Val144fs Likely pathogenic ★ same condition
UBAP1 p.Asp99fs Pathogenic same condition
UBAP1 p.Glu97fs Pathogenic same condition
UBAP1 p.Leu121fs Pathogenic same condition
UBAP1 p.Lys143fs Pathogenic ★★ same condition
UBAP1 p.Glu455fs Uncertain significance ★★ same condition
UBAP1 c.-20C>T Likely pathogenic ★ same condition
UBAP1 p.Asp158_Phe159insTer Pathogenic ★ 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/ubap1-p-cys161fs (accessed [today's date]).

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