SACS p.Pro4435fs
c.13304del · VCV3236275
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
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 | escapes | premature termination codon in the last exon (10 of 10) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -0.34 | GERP -3.7, phastCons 0.001 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- SACS
- Protein
- p.Pro4435fs
- Coding
- c.13304del
- MANE Select
- NM_014363
- Type
- Deletion
- Location
- chr13:23330572 (GRCh38)
- Gene constraint
- LOEUF 0.644 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Disease context
Charlevoix-Saguenay spastic ataxia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor 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-pro4435fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown