Is SYNJ1 p.Ala44Ser (c.130G>T) pathogenic?

SYNJ1 p.Ala44Ser (c.130G>T) is classified Uncertain significance in SYNJ1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-28). Very rare (popmax 0.00173%, amr); Associated with developmental and epileptic encephalopathy, 53.

How common is SYNJ1 p.Ala44Ser (c.130G>T) in the general population?

SYNJ1 p.Ala44Ser (c.130G>T) is very rare (popmax 0.00173%, amr) (gnomAD).

SYNJ1 p.Ala44Ser

Q: What condition is associated with SYNJ1 p.Ala44Ser (c.130G>T)?

SYNJ1 p.Ala44Ser (c.130G>T) is associated with developmental and epileptic encephalopathy, 53, early-onset Parkinson disease 20 (ClinVar).

c.130G>T · rs771635470 · VCV1437886

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00173%, amr)

Conditions

developmental and epileptic encephalopathy, 53

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.551	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 80 kb · p 9.8e-17 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00173% Admixed American · 1/57,886 alleles

Filtering AF 0.000372% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00027%

Overall 0.000711% 11/1,546,816 alleles · very rare exomes 11/1,394,582 · genomes 0/152,234 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00173%	57,886
African / African-American	0.00135%	74,142
European (non-Finnish)	0.000791%	126,342

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: SYNJ1
Protein: p.Ala44Ser
Coding: c.130G>T
MANE Select: NM_203446
dbSNP: rs771635470
Type: single nucleotide variant
Location: chr21:32702042 (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-ala44ser (accessed [today's date]).

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