Is SPAST p.Ser413Ter (c.1238C>A) pathogenic?

SPAST p.Ser413Ter (c.1238C>A) is classified Pathogenic/Likely pathogenic in SPAST (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-12-23). No allele count reported in gnomAD v4.1 (AN 1,599,586); Associated with SPAST-related disorder.

What condition is associated with SPAST p.Ser413Ter (c.1238C>A)?

SPAST p.Ser413Ter (c.1238C>A) is associated with SPAST-related disorder, hereditary spastic paraplegia 4 (ClinVar).

How common is SPAST p.Ser413Ter (c.1238C>A) in the general population?

SPAST p.Ser413Ter (c.1238C>A) is no allele count reported in gnomAD v4.1 (AN 1,599,586) (gnomAD).

SPAST p.Ser413Ter

c.1238C>A · rs1553317045 · VCV1070822

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,599,586)

Conditions

SPAST-related disorder

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 9 of 17
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.25	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Overall
CADD	46.0	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

No allele count reported in gnomAD v4.1 (AN 1,599,586). 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.Ser413Ter
Coding: c.1238C>A
MANE Select: NM_014946
dbSNP: rs1553317045
Type: single nucleotide variant
Location: chr2:32128472 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI 0.11 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 7 PDB
Residue 413: the 'sufficient for microtubule severing' region; a UniProt-annotated variant site (in spg4)

Full SPAST gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SPAST-related disorder

Also linked: hereditary spastic paraplegia 4

Similar variants

SPAST p.Ser413Leu Pathogenic ★ same residue
SPAST p.Ser413Thr Uncertain significance ★ ⚠ 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

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-ser413ter (accessed [today's date]).

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