Is SPART p.Pro409= (c.1227A>G) pathogenic?

SPART p.Pro409= (c.1227A>G) is classified Likely benign in SPART (ClinVar, Single submitter, 1 submitter; last evaluated 2017-06-19). Absent from gnomAD v4.1; Associated with Troyer syndrome.

What condition is associated with SPART p.Pro409= (c.1227A>G)?

SPART p.Pro409= (c.1227A>G) is associated with Troyer syndrome (ClinVar).

How common is SPART p.Pro409= (c.1227A>G) in the general population?

SPART p.Pro409= (c.1227A>G) is absent from gnomAD v4.1 (gnomAD).

How is Autosomal recessive spastic paraplegia type 20 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SPART p.Pro409=

c.1227A>G · rs1555261871 · VCV461201

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Troyer syndrome

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 0.84	GERP 0.65, phastCons 1
Overall
CADD	11.0	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: SPART
Protein: p.Pro409=
Coding: c.1227A>G
MANE Select: NM_015087
dbSNP: rs1555261871
Type: single nucleotide variant
Location: chr13:36326636 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.03 · 2 PDB

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

Disease context

Troyer syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive spastic paraplegia type 20 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

SPART p.Pro409Ala Uncertain significance ★★ ⚠ same residue
SPART p.Pro409Leu Uncertain significance ★ ⚠ same residue
SPART p.Arg457Ter Pathogenic ★★ same condition
SPART p.Gln229Ter Pathogenic/Likely pathogenic ★★ same condition
SPART p.Arg249Gln Uncertain significance ★★ ⚠ same condition
SPART p.Asn582Ile Uncertain significance ★★ ⚠ same condition
SPART p.Asp652Asn Uncertain significance ★★ ⚠ same condition
SPART p.Glu40Ala 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/spart-p-pro409 (accessed [today's date]).

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