SYN1 p.Pro655fs
c.1962del · rs1556857412 · VCV547077
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | escapes | premature termination codon within the last 50 nt of the penultimate exon (12 of 13, 20 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
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.Pro655fs
- Coding
- c.1962del
- MANE Select
- NM_006950
- dbSNP
- rs1556857412
- Type
- Deletion
- Location
- chrX:47574022 (GRCh38)
- Structure
- AlphaFold pLDDT 69.86
- Residue 655
- the 'disordered' region; 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 'd; pro-rich linker' region
Similar variants
- SYN1 p.Pro655Leu Uncertain significance ★★ ⚠ same residue
- SYN1 p.Asn334fs Pathogenic ★★ same type
- SYN1 p.Met1fs Pathogenic/Likely pathogenic ★★ same type
- SYN1 p.His38_Ala42del Uncertain significance ★★ same type
- SYN1 c.1056-14_1056-8del Benign ★★ same type
- SYN1 c.980+43_981del Pathogenic ★ same type
- SYN1 p.Ala577fs Pathogenic ★ same type
- SYN1 p.Ala676fs Likely 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-pro655fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown