SPAST p.Ser545Ter
c.1634C>G · rs869312949 · VCV225068
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
1
Inborn genetic diseases
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 15 of 17 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.4 | 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
- SPAST
- Protein
- p.Ser545Ter
- Coding
- c.1634C>G
- MANE Select
- NM_014946
- dbSNP
- rs869312949
- Type
- single nucleotide variant
- Location
- chr2:32144954 (GRCh38)
- Gene constraint
- LOEUF 0.69 · pLI 0.11 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.03 · 7 PDB
- Residue 545
- a UniProt-annotated variant site (in spg4); the 'sufficient for microtubule severing' region
Similar variants
- SPAST p.Ser545Leu Pathogenic/Likely pathogenic ★★ same residue
- SPAST p.Asn487Asp Likely pathogenic ★★ same condition
- SPAST p.Glu356Lys Pathogenic/Likely pathogenic ★★ same condition
- SPAST p.Met390Val Pathogenic ★★ ⚠ same condition
- SPAST p.Ala394Val Uncertain significance ★★ ⚠ same condition
- SPAST p.Ala39Asp Uncertain significance ★★ ⚠ same condition
- SPAST p.Cys220Trp Uncertain significance ★★ ⚠ same condition
- SPAST p.Glu602Ala Uncertain significance ★★ ⚠ 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-ser545ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown