Is SACS p.Phe447fs (c.1339_1340del) pathogenic?

SACS p.Phe447fs (c.13391340del) is classified Likely pathogenic in SACS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). Associated with Charlevoix-Saguenay spastic ataxia.

What condition is associated with SACS p.Phe447fs (c.1339_1340del)?

SACS p.Phe447fs (c.1339_1340del) is associated with Charlevoix-Saguenay spastic ataxia (ClinVar).

SACS p.Phe447fs

Q: How is Autosomal recessive spastic ataxia of Charlevoix-Saguenay inherited?

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

c.1339_1340del · VCV4061085

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Charlevoix-Saguenay spastic ataxia

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 0.64	GERP -3.9, phastCons 0.94

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

Variant & gene context

Gene: SACS
Protein: p.Phe447fs
Coding: c.1339_1340del
MANE Select: NM_014363
Type: Deletion
Location: chr13:23355272 (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

Charlevoix-Saguenay spastic ataxia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive spastic ataxia of Charlevoix-Saguenay (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy

Similar variants

SACS p.Ala1723fs Pathogenic/Likely pathogenic ★★ same condition
SACS p.Ala2208fs Pathogenic/Likely pathogenic ★★ same condition
SACS p.Arg624fs Pathogenic/Likely pathogenic ★★ same condition
SACS p.Arg919fs Pathogenic/Likely pathogenic ★★ same condition
SACS p.Asn1025fs Pathogenic/Likely pathogenic ★★ same condition
SACS p.Asn1586fs Pathogenic ★★ same condition
SACS p.Asn1616fs Likely pathogenic ★★ same condition
SACS p.Asn2380fs 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-phe447fs (accessed [today's date]).

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