SYN1 p.Ser162Pro
c.484T>C · VCV4950323
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9924 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9924 | likely pathogenic |
|---|---|---|
| REVEL | 0.163 | moderately benign-leaning |
| SaProt | LLR -14.66 | damaging |
| ⇒ AlphaMissense and SaProt call this damaging; REVEL does not. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 9.1 | GERP 1.3, phastCons 1 |
| Regional constraint | o/e 0.70 | unconstrained · MANE · 45 kb · p 1.4e-10 · regional, not allelic |
| Overall | ||
| CADD | 25.0 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- SYN1
- Protein
- p.Ser162Pro
- Coding
- c.484T>C
- MANE Select
- NM_006950
- Type
- single nucleotide variant
- Location
- chrX:47606988 (GRCh38)
- Structure
- AlphaFold pLDDT 69.86
- Residue 162
- the 'c; actin-binding and synaptic-vesicle binding' region
Similar variants
- SYN1 p.Ser162Phe Uncertain significance ★ ⚠ same residue
- 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
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-ser162pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown