SYNJ1 p.Pro782=
c.2346G>A · rs61753644 · VCV478333
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
rare (popmax 0.142%, nfe)
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 | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -7.2 | GERP -3.7 |
| Overall | ||
| CADD | 2.101 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.142%
European (non-Finnish) · 1,675/1,179,902 alleles
Filtering AF
0.136%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.134%
Overall
0.113%
1,820/1,613,830 alleles · rare
exomes 1,694/1,461,574 · genomes 126/152,256 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.142% | 704 |
| Finnishnot grpmax-eligible | 0.1% | 1,000 |
| Remaining individualsnot grpmax-eligible | 0.0832% | 1,202 |
| African / African-American | 0.0253% | 3,947 |
| Admixed American | 0.0167% | 5,995 |
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.Pro782=
- Coding
- c.2346G>A
- MANE Select
- NM_203446
- dbSNP
- rs61753644
- Type
- single nucleotide variant
- Location
- chr21:32657831 (GRCh38)
- Gene constraint
- LOEUF 0.539 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.09 · 5 PDB
- Residue 782
- the 5-ppase domain
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-pro782 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown