SYN1 p.Ser704=
c.2112C>T · rs1227806166 · VCV994515
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00175%, sas)
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 6.4 | phastCons 1 |
| Overall | ||
| CADD | 8.758 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00175%
South Asian · 1/56,991 alleles
Overall
8.25e-05%
1/1,211,601 alleles · very rare
exomes 1/1,098,067 · genomes 0/113,534 · 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
- SYN1
- Protein
- p.Ser704=
- Coding
- c.2112C>T
- MANE Select
- NM_006950
- dbSNP
- rs1227806166
- Type
- single nucleotide variant
- Location
- chrX:47572870 (GRCh38)
- Structure
- AlphaFold pLDDT 69.86
- Residue 704
- a UniProt-annotated variant site (in xlid50; affects excitatory and inhibitory synaptic transmission leading to neuronal hyperexcitability; fails to rescue defective synaptic vesicle exocytosis in syn1-knockout mouse neurons; results in severely decreased phosphorylation by camk2 and mapk1; results in delayed axon elongation when tested in syn1-knockout mouse neurons; severely reduced interaction with syn2; has no effect on protein targeting to presynapse); the 'e' region
Similar variants
- SYN1 c.528-2A>T Pathogenic/Likely pathogenic ★★ same type
- SYN1 c.838-2A>G Likely pathogenic ★★ same type
- SYN1 p.Arg234Ter Pathogenic ★★ same type
- SYN1 p.Arg420Gln Likely pathogenic ★★ ⚠ same type
- SYN1 p.Arg422Ter Pathogenic ★★ same type
- SYN1 p.Gln249Ter Pathogenic/Likely pathogenic ★★ same type
- SYN1 p.Gln483Ter Pathogenic ★★ same type
- SYN1 p.Gln555Ter Pathogenic ★★ same type
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/syn1-p-ser704 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown