Is SPAST p.Pro233fs (c.698del) pathogenic?

SPAST p.Pro233fs (c.698del) is classified Pathogenic in SPAST (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-28). No gnomAD frequency available for this variant; Associated with hereditary spastic paraplegia 4.

What condition is associated with SPAST p.Pro233fs (c.698del)?

SPAST p.Pro233fs (c.698del) is associated with hereditary spastic paraplegia 4 (ClinVar).

How common is SPAST p.Pro233fs (c.698del) in the general population?

SPAST p.Pro233fs (c.698del) is no gnomAD frequency available for this variant (gnomAD).

How is Autosomal dominant spastic paraplegia type 4 inherited?

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

SPAST p.Pro233fs

c.698del · rs1573118105 · VCV650603

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

hereditary spastic paraplegia 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 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 6.1	GERP 1.6, phastCons 1

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: SPAST
Protein: p.Pro233fs
Coding: c.698del
MANE Select: NM_014946
dbSNP: rs1573118105
Type: Deletion
Location: chr2:32114652 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI 0.11 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 7 PDB
Residue 233: 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

hereditary spastic paraplegia 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant spastic paraplegia type 4 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 1 000 000 (Portugal)

Similar variants

SPAST c.1174-1del Pathogenic ★★ same condition
SPAST c.1413+3_1413+6del Pathogenic/Likely pathogenic ★★ same condition
SPAST c.1493+2_1493+5del Pathogenic/Likely pathogenic ★★ same condition
SPAST c.(?_1729 Pathogenic ★★ same condition
SPAST p.Ala188fs Pathogenic ★★ same condition
SPAST p.Ala394fs Pathogenic ★★ same condition
SPAST p.Ala96fs Pathogenic ★★ same condition
SPAST p.Gln280fs 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-pro233fs (accessed [today's date]).

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