Is SACS p.Lys115Ter (c.343A>T) pathogenic?

SACS p.Lys115Ter (c.343A>T) is classified Likely pathogenic in SACS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-08). Absent from gnomAD v4.1; Associated with Charlevoix-Saguenay spastic ataxia.

What condition is associated with SACS p.Lys115Ter (c.343A>T)?

SACS p.Lys115Ter (c.343A>T) is associated with Charlevoix-Saguenay spastic ataxia (ClinVar).

How common is SACS p.Lys115Ter (c.343A>T) in the general population?

SACS p.Lys115Ter (c.343A>T) is absent from gnomAD v4.1 (gnomAD).

SACS p.Lys115Ter

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.343A>T · rs2542458038 · VCV1726003

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Charlevoix-Saguenay spastic ataxia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 10
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SACS
Protein: p.Lys115Ter
Coding: c.343A>T
MANE Select: NM_014363
dbSNP: rs2542458038
Type: single nucleotide variant
Location: chr13:23368404 (GRCh38)
Gene constraint: LOEUF 0.644 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 115: 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 c.2093+1G>A Likely pathogenic ★★ same condition
SACS c.604+1G>A Likely pathogenic ★★ same condition
SACS p.Ala4074Pro Pathogenic ★★ same condition
SACS p.Arg1575Pro Pathogenic ★★ same condition
SACS p.Arg1645Gln Likely pathogenic ★★ same condition
SACS p.Arg1645Ter Pathogenic ★★ same condition
SACS p.Arg1877Ter Pathogenic/Likely pathogenic ★★ same condition
SACS p.Arg1907Ter 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-lys115ter (accessed [today's date]).

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