SYNJ1 p.Val769=
c.2307T>C · VCV4788245
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00269%, afr)
Conditions
2
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 2.9 | GERP -0.73, phastCons 1 |
| Overall | ||
| CADD | 10.25 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00269%
African / African-American · 2/74,408 alleles
Filtering AF
0.000446%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000167%
Overall
0.000124%
2/1,607,526 alleles · very rare
exomes 0/1,455,400 · genomes 2/152,126 · 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.Val769=
- Coding
- c.2307T>C
- MANE Select
- NM_203446
- Type
- single nucleotide variant
- Location
- chr21:32657870 (GRCh38)
- Gene constraint
- LOEUF 0.539 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.09 · 5 PDB
- Residue 769
- the 5-ppase domain; a β-strand
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-val769 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown