SNCA (Alpha-synuclein) variants and mutations
SNCA (also known as Alpha-synuclein) is a human protein-coding gene encoding an alpha-synuclein protein. Alpha-synuclein is a neuronal protein that supports synaptic-vesicle trafficking, priming, and neurotransmitter release. Misfolded or aggregated alpha-synuclein is a defining feature of Parkinson disease and Lewy-body disorders. This analysis covers 12 SNCA variants and mutations. Of these, 100% have computational variant effect predictions. Disease context includes Hereditary late-onset Parkinson disease, Young adult-onset Parkinsonism, and Parkinson disease. Example SNCA variants include A30P, E46K, and H50Q.
Variant analysis overview
- Gene: SNCA
- Protein: Alpha-synuclein
- UniProt accession: P37840
- Organism: Homo sapiens
- Variants analyzed: 12
- Variant scope: all variants
- Completed: 2026-06-10
Variant and mutation evidence
- Variant composition: 4 natural variant; 1 stop lost; 4 missense variants; 1 frameshift variants; 2 synonymous variants
- Prediction scores: 12 variants have prediction scores (100% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Hereditary late-onset Parkinson disease, Young adult-onset Parkinsonism, Parkinson disease, Lewy body dementia, AL amyloidosis, insomnia, REM sleep behavior disorder, parkinsonian-pyramidal syndrome, Cachexia, Anxiety, Abnormality of the skeletal system, schizophrenia.
Protein structure and variant hotspots
- Protein features: 2 binding sites; 4 post-translational modification sites.
- PTM context: 1 variants overlap post-translational modification sites.
- Experimental data: 140 protein positions have experimental scores. Source: Deep Mutational Scanning of alpha-Synuclein based on Toxicity in Yeast Treated with Melatonin, Deep Mutational Scanning of alpha-Synuclein based on Toxicity in Yeast, Deep Mutational Scanning of alpha-Synuclein based on Toxicity in Yeast Treated with Dopamine.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, PharmGKB, MaveDB, LitVar.
Notable SNCA variants
Examples include A30P, E46K, H50Q, A53T, M127L, P128P, S129F, G132S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A30P (p.Ala30Pro), rs104893878, AlphaMissense 0.99, MetaLR 0.81, Conflicting interpretations, Lewy body dementia; Autosomal dominant Parkinson disease 1; Autosomal dominant P
- E46K (p.Glu46Lys), rs104893875, AlphaMissense 0.55, MetaLR 0.55, Pathogenic, Autosomal dominant Parkinson disease 1; Lewy body dementia
- H50Q (p.His50Gln), rs201106962, REVEL 0.43, CADD 7.08, Uncertain significance, Lewy body dementia; Autosomal dominant Parkinson disease 1; Autosomal dominant P
- A53T (p.Ala53Thr), rs104893877, AlphaMissense 0.05, MetaLR 0.18, Pathogenic, Autosomal dominant Parkinson disease 1; Lewy body dementia; Autosomal dominant P
- M127L (p.Met127Leu), rs575502104, gnomAD 4-89702339-T-A, CADD 1.33
- P128P (p.Pro128Pro), rs1215212302, gnomAD 4-89702379-T-C, CADD 8.33
- S129F (p.Ser129Phe), rs756636909, gnomAD 4-89702326-G-A, CADD 0.20
- G132S (p.Gly132Ser), rs1723915037, gnomAD 4-89702348-C-T, CADD 1.17
- Q134Q (p.Gln134Gln), rs1478960449, gnomAD 4-89702361-C-T, CADD 0.28
- E137K (p.Glu137Lys), rs1723915305, gnomAD 4-89702372-C-T, CADD 5.87
- A140V (p.Ala140Val), rs1560475704, gnomAD 4-89702336-ACATGG, CADD 0.68
Public SNCA analysis runs
- SNCA analysis run — SNCA (12 variants) — completed 2026-06-10