Is SYNJ1 p.Ser511= (c.1533A>G) pathogenic?

SYNJ1 p.Ser511= (c.1533A>G) is classified Uncertain significance in SYNJ1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-15). Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 53.

How common is SYNJ1 p.Ser511= (c.1533A>G) in the general population?

SYNJ1 p.Ser511= (c.1533A>G) is absent from gnomAD v4.1 (gnomAD).

SYNJ1 p.Ser511=

Q: What condition is associated with SYNJ1 p.Ser511= (c.1533A>G)?

SYNJ1 p.Ser511= (c.1533A>G) is associated with developmental and epileptic encephalopathy, 53, early-onset Parkinson disease 20 (ClinVar).

c.1533A>G · rs2516675789 · VCV2021269

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

developmental and epileptic encephalopathy, 53

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.40	donor loss · deltas
Pangolin	Δ0.45	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Overall
CADD	19.9	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.Ser511=
Coding: c.1533A>G
MANE Select: NM_203446
dbSNP: rs2516675789
Type: single nucleotide variant
Location: chr21:32676333 (GRCh38)
Gene constraint: LOEUF 0.539 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.09 · 5 PDB

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

Disease context

developmental and epileptic encephalopathy, 53 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: early-onset Parkinson disease 20

Similar variants

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
SYNJ1 p.Gln748Ter Pathogenic/Likely pathogenic ★★ same condition
SYNJ1 c.-42A>G 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/synj1-p-ser511 (accessed [today's date]).

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