Is SYNJ1 p.Pro905= (c.2715A>G) pathogenic?

SYNJ1 p.Pro905= (c.2715A>G) is classified Likely benign in SYNJ1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-18). Ultra-rare (popmax 0.011%, sas); Associated with developmental and epileptic encephalopathy, 53.

How common is SYNJ1 p.Pro905= (c.2715A>G) in the general population?

SYNJ1 p.Pro905= (c.2715A>G) is ultra-rare (popmax 0.011%, sas) (gnomAD).

SYNJ1 p.Pro905=

Q: What condition is associated with SYNJ1 p.Pro905= (c.2715A>G)?

SYNJ1 p.Pro905= (c.2715A>G) is associated with developmental and epileptic encephalopathy, 53, early-onset Parkinson disease 20 (ClinVar).

c.2715A>G · rs771107718 · VCV1536150

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Conditions

developmental and epileptic encephalopathy, 53

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 -0.39	GERP 0.57, phastCons 0.22
Overall
CADD	9.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/91,088 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.00062% 10/1,614,030 alleles · ultra-rare exomes 9/1,461,826 · genomes 1/152,204 · joint denominator

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.Pro905=
Coding: c.2715A>G
MANE Select: NM_203446
dbSNP: rs771107718
Type: single nucleotide variant
Location: chr21:32656767 (GRCh38)
Gene constraint: LOEUF 0.539 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.09 · 5 PDB
Residue 905: a turn; the rrm domain

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 p.Pro905Thr 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
SYNJ1 p.Gln748Ter 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-pro905 (accessed [today's date]).

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