SYNJ1 p.Ser1069Gly
c.3205A>G · rs149817769 · VCV478339
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.276%, 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. | ||
| REVEL | 0.372 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 6.2 | GERP 1.2, phastCons 1 |
| Regional constraint | o/e 0.99 | unconstrained · MANE · 12 kb · p 0.77 · regional, not allelic |
| Overall | ||
| CADD | 23.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.276%
African / African-American · 207/75,044 alleles
Filtering AF
0.245%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.233%
Overall
0.0138%
223/1,614,168 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.276% | 363 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,945 |
| Admixed American | 0.0117% | 8,575 |
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.Ser1069Gly
- Coding
- c.3205A>G
- MANE Select
- NM_203446
- dbSNP
- rs149817769
- Type
- single nucleotide variant
- Location
- chr21:32646435 (GRCh38)
- Gene constraint
- LOEUF 0.539 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.09 · 5 PDB
- Residue 1069
- the 'disordered' region
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-ser1069gly (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown