Is SPAST p.Arg235fs (c.703del) pathogenic?

SPAST p.Arg235fs (c.703del) is classified Pathogenic in SPAST (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-06). Associated with SPAST-related disorder.

What condition is associated with SPAST p.Arg235fs (c.703del)?

SPAST p.Arg235fs (c.703del) is associated with SPAST-related disorder (ClinVar).

SPAST p.Arg235fs

c.703del · VCV4954566

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

SPAST-related disorder

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 haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 5 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1

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

Variant & gene context

Gene: SPAST
Protein: p.Arg235fs
Coding: c.703del
MANE Select: NM_014946
Type: Deletion
Location: chr2:32114654 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI 0.11 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 7 PDB
Residue 235: the 'disordered' region; the 'sufficient for microtubule severing' region; a UniProt-annotated variant site (in spg4); the 'required for interaction with rtn1' region

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

Disease context

SPAST-related disorder

Similar variants

SPAST c.1413+3_1413+6del Pathogenic/Likely pathogenic ★★ same condition
SPAST p.Ile592fs Pathogenic/Likely pathogenic ★★ same condition
SPAST p.Phe403fs Pathogenic/Likely pathogenic ★★ same condition
SPAST c.1004+3_1004+5del Likely pathogenic ★ same condition
SPAST p.Arg117fs Likely pathogenic ★ same condition
SPAST p.Asp134fs Likely pathogenic ★ same condition
SPAST p.Asp237fs Likely pathogenic ★ same condition
SPAST p.Ile561fs Likely 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/spast-p-arg235fs (accessed [today's date]).

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