Is SACS p.Phe299fs (c.896_898delinsCT) pathogenic?

SACS p.Phe299fs (c.896898delinsCT) is classified Likely pathogenic in SACS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-14). No gnomAD frequency available for this variant; Associated with Charlevoix-Saguenay spastic ataxia.

What condition is associated with SACS p.Phe299fs (c.896_898delinsCT)?

SACS p.Phe299fs (c.896_898delinsCT) is associated with Charlevoix-Saguenay spastic ataxia (ClinVar).

How common is SACS p.Phe299fs (c.896_898delinsCT) in the general population?

SACS p.Phe299fs (c.896_898delinsCT) is no gnomAD frequency available for this variant (gnomAD).

SACS p.Phe299fs

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.896_898delinsCT · rs2542401788 · VCV2678575

Likely pathogenic Single submitter

Classification

Likely 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

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 0.47	GERP -2.6, phastCons 0.014

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: SACS
Protein: p.Phe299fs
Coding: c.896_898delinsCT
MANE Select: NM_014363
dbSNP: rs2542401788
Type: Indel
Location: chr13:23355714 (GRCh38)
Gene constraint: LOEUF 0.644 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 299: an α-helix

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.Asn3487_Leu3488delinsLysIle Uncertain significance ★★ same condition
SACS p.Ala155fs Likely pathogenic ★ same condition
SACS p.Arg730fs Likely pathogenic ★ same condition
SACS p.Glu2745fs Likely pathogenic ★ same condition
SACS p.Gly2090Ter Likely pathogenic ★ same condition
SACS p.Gly65fs Likely pathogenic ★ same condition
SACS p.His1227Ter Likely pathogenic ★ same condition
SACS p.Leu3525Ter 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-phe299fs (accessed [today's date]).

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