Is SACS p.Pro488fs (c.1463del) pathogenic?

SACS p.Pro488fs (c.1463del) is classified Pathogenic in SACS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-22). Associated with Spastic paraplegia.

What condition is associated with SACS p.Pro488fs (c.1463del)?

SACS p.Pro488fs (c.1463del) is associated with Spastic paraplegia (ClinVar).

SACS p.Pro488fs

c.1463del · VCV3729343

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Spastic paraplegia

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 8 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -11	GERP -3.9

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

Variant & gene context

Gene: SACS
Protein: p.Pro488fs
Coding: c.1463del
MANE Select: NM_014363
Type: Deletion
Location: chr13:23355149 (GRCh38)
Gene constraint: LOEUF 0.644 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

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

Disease context

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

Similar variants

SACS p.Pro488Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
SACS p.Pro488= Likely benign ★ same residue
SACS p.Ala2208fs Pathogenic/Likely pathogenic ★★ same condition
SACS p.Arg4412fs Pathogenic/Likely pathogenic ★★ same condition
SACS p.Asn2380fs Pathogenic/Likely pathogenic ★★ same condition
SACS p.Asn2615fs Pathogenic/Likely pathogenic ★★ same condition
SACS p.Asp1498fs Pathogenic/Likely pathogenic ★★ same condition
SACS p.Asp1903fs Pathogenic/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/sacs-p-pro488fs (accessed [today's date]).

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