SYNJ1 p.Pro1249=
c.3747G>C · rs138579227 · VCV2033156
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 6.2e-05%)
Conditions
2
developmental and epileptic encephalopathy, 53
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.036 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.24 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -2.1 | GERP -3.3 |
| Overall | ||
| CADD | 1.382 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.2e-05%
Overall
6.2e-05%
1/1,613,724 alleles · very rare
exomes 1/1,461,640 · genomes 0/152,084 · 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.Pro1249=
- Coding
- c.3747G>C
- MANE Select
- NM_203446
- dbSNP
- rs138579227
- Type
- single nucleotide variant
- Location
- chr21:32639076 (GRCh38)
- Gene constraint
- LOEUF 0.539 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.09 · 5 PDB
- Residue 1249
- the 'disordered' region
Similar variants
- SYNJ1 p.Pro1249Leu Conflicting classifications of pathogenicity ★ 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-pro1249 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown