SPAST p.Ser44Ter
c.131C>A · VCV3720309
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 in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 1 of 17 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.4 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 38.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
No allele count reported in gnomAD v4.1 (AN 1,612,230). 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
- SPAST
- Protein
- p.Ser44Ter
- Coding
- c.131C>A
- MANE Select
- NM_014946
- Type
- single nucleotide variant
- Location
- chr2:32063962 (GRCh38)
- Gene constraint
- LOEUF 0.69 · pLI 0.11 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.03 · 7 PDB
- Residue 44
- a UniProt-annotated variant site (in spg4); a UniProt-annotated variant site (acts as a disease modifier; patients carrying a mutated allele of spastin and l-44 on the other allele are affected by severe spastic paraplegia with an early age of onset; may decrease the activity of the alternative promoter which directs the synthesis of isoform 3 and isoform 4); the 'required for interaction with rtn1' region; the 'required for midbody localization' region; the 'required for interaction with atl1' region; the 'required for nuclear localization' region
Disease context
hereditary spastic paraplegia 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Autosomal dominant spastic paraplegia type 4 (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Adolescent, Adult, Childhood, Infancy
- Prevalence
- 1-9 / 1 000 000 (Portugal)
Similar variants
- SPAST p.Ser44= Likely benign ★ same residue
- SPAST c.1004+1G>C Pathogenic/Likely pathogenic ★★ same condition
- SPAST c.1004+1G>T Pathogenic ★★ same condition
- SPAST c.1004+2T>G Pathogenic ★★ same condition
- SPAST c.1098+1G>A Pathogenic ★★ same condition
- SPAST c.1099-1G>A Pathogenic ★★ same condition
- SPAST c.1099-2A>C Pathogenic/Likely pathogenic ★★ same condition
- SPAST c.1173+1G>A 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/spast-p-ser44ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown