Is SYNJ1 p.Arg250= (c.750A>G) pathogenic?

SYNJ1 p.Arg250= (c.750A>G) is classified Likely benign in SYNJ1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-19). Absent from gnomAD v4.1; Associated with early-onset Parkinson disease 20.

What condition is associated with SYNJ1 p.Arg250= (c.750A>G)?

SYNJ1 p.Arg250= (c.750A>G) is associated with early-onset Parkinson disease 20, developmental and epileptic encephalopathy, 53 (ClinVar).

How common is SYNJ1 p.Arg250= (c.750A>G) in the general population?

SYNJ1 p.Arg250= (c.750A>G) is absent from gnomAD v4.1 (gnomAD).

How is Young-onset Parkinson disease inherited?

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

SYNJ1 p.Arg250=

c.750A>G · rs2516834972 · VCV2935267

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

early-onset Parkinson disease 20

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.61	GERP -3.7, phastCons 0.014
Overall
CADD	9.088	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: SYNJ1
Protein: p.Arg250=
Coding: c.750A>G
MANE Select: NM_203446
dbSNP: rs2516834972
Type: single nucleotide variant
Location: chr21:32694267 (GRCh38)
Gene constraint: LOEUF 0.539 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.09 · 5 PDB
Residue 250: the sac domain

Full SYNJ1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

early-onset Parkinson disease 20 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 53

For Young-onset Parkinson disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

SYNJ1 p.Arg250Ter Pathogenic ★ same residue
SYNJ1 p.Arg250Gln Uncertain significance ★ same residue
SYNJ1 c.1201-2A>G Likely pathogenic ★★ same condition
SYNJ1 c.2461+2T>C Likely pathogenic ★★ same condition
SYNJ1 c.3478+1G>A Likely pathogenic ★★ same condition
SYNJ1 p.Arg219Gln Pathogenic ★★ same condition
SYNJ1 p.Arg534Ter Pathogenic/Likely pathogenic ★★ same condition
SYNJ1 p.Arg709Ter 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/synj1-p-arg250 (accessed [today's date]).

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