SYNJ1 p.Pro15Ser
c.43C>T · rs61755328 · VCV445927
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.45%, 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 | 0.7 | pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 9.5 | GERP 3.7, phastCons 1 |
| Regional constraint | o/e 0.76 | unconstrained · MANE · 80 kb · p 9.8e-17 · regional, not allelic |
| Overall | ||
| CADD | 24.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.45%
African / African-American · 1,087/75,008 alleles
Filtering AF
1.38%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.35%
Overall
0.0755%
1,218/1,614,100 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.45% | 69 |
| Remaining individualsnot grpmax-eligible | 0.117% | 856 |
| Admixed American | 0.0666% | 1,500 |
| Middle Eastern | 0.033% | 3,031 |
| European (non-Finnish) | 0.00136% | 73,751 |
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.Pro15Ser
- Coding
- c.43C>T
- MANE Select
- NM_203446
- dbSNP
- rs61755328
- Type
- single nucleotide variant
- Location
- chr21:32726853 (GRCh38)
- Gene constraint
- LOEUF 0.539 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.09 · 5 PDB
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-pro15ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown