Is SPART p.Pro209= (c.627G>A) pathogenic?

SPART p.Pro209= (c.627G>A) is classified Conflicting classifications of pathogenicity in SPART (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-03-15). Ultra-rare (popmax 0.0278%, nfe); Associated with Troyer syndrome.

What condition is associated with SPART p.Pro209= (c.627G>A)?

SPART p.Pro209= (c.627G>A) is associated with Troyer syndrome (ClinVar).

How common is SPART p.Pro209= (c.627G>A) in the general population?

SPART p.Pro209= (c.627G>A) is ultra-rare (popmax 0.0278%, nfe) (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.Pro209=

c.627G>A · rs370385005 · VCV311770

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0278%, nfe)

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 -0.83	GERP -3
Overall
CADD	3.842	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0278% European (non-Finnish) · 328/1,180,014 alleles

Filtering AF 0.0253% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0243%

Overall 0.0219% 354/1,614,088 alleles · ultra-rare exomes 340/1,461,846 · genomes 14/152,242 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0278%	3,598
Remaining individualsnot grpmax-eligible	0.0224%	4,465
African / African-American	0.0107%	9,377
South Asian	0.00329%	30,359
East Asian	0.00223%	44,870

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SPART
Protein: p.Pro209=
Coding: c.627G>A
MANE Select: NM_015087
dbSNP: rs370385005
Type: single nucleotide variant
Location: chr13:36335204 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.03 · 2 PDB
Residue 209: the 'ubiquitin-binding region (ubr) domain' region

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.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
SPART p.Glu41Asp Uncertain significance ★★ ⚠ same condition
SPART p.Gly98Ser 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-pro209 (accessed [today's date]).

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