Is SPAST p.Pro286= (c.858T>C) pathogenic?

SPAST p.Pro286= (c.858T>C) is classified Likely benign in SPAST (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-05). Absent from gnomAD v4.1.

How common is SPAST p.Pro286= (c.858T>C) in the general population?

SPAST p.Pro286= (c.858T>C) is absent from gnomAD v4.1 (gnomAD).

SPAST p.Pro286=

c.858T>C · rs2465835684 · VCV3251485

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.6	GERP -2.9, phastCons 0.29
Overall
CADD	2.302	PHRED · no single calibrated threshold — expert panels disagree

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.Pro286=
Coding: c.858T>C
MANE Select: NM_014946
dbSNP: rs2465835684
Type: single nucleotide variant
Location: chr2:32114813 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI 0.11 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 7 PDB
Residue 286: the 'sufficient for microtubule severing' region; the 'required for interaction with microtubules and microtubule severing' region; the 'disordered' region; a UniProt-annotated variant site (in spg4); the 'required for interaction with rtn1' region

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

Similar variants

SPAST p.Pro286Leu Uncertain significance ★ ⚠ same residue
SPAST p.Pro286Thr Uncertain significance ★ ⚠ same residue
SPAST p.Pro286fs Pathogenic ★ same residue
SPAST c.1004+1G>C Pathogenic/Likely pathogenic ★★ same type
SPAST c.1004+1G>T Pathogenic ★★ same type
SPAST c.1004+2T>G Pathogenic ★★ same type
SPAST c.1098+1G>A Pathogenic ★★ same type
SPAST c.1099-1G>A Pathogenic ★★ same type

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-pro286 (accessed [today's date]).

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