Is SNCA p.Glu83= (c.249G>A) pathogenic?

SNCA p.Glu83= (c.249G>A) is classified Likely benign in SNCA (ClinVar, Single submitter, 1 submitter; last evaluated 2017-04-27). Absent from gnomAD v4.1; Associated with Parkinson Disease, Dominant.

What condition is associated with SNCA p.Glu83= (c.249G>A)?

SNCA p.Glu83= (c.249G>A) is associated with Parkinson Disease, Dominant (ClinVar).

How common is SNCA p.Glu83= (c.249G>A) in the general population?

SNCA p.Glu83= (c.249G>A) is absent from gnomAD v4.1 (gnomAD).

SNCA p.Glu83=

c.249G>A · rs1737224483 · VCV907548

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Parkinson Disease, Dominant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.5	GERP -2.6, phastCons 1
Overall
CADD	9.033	PHRED · no single calibrated threshold — expert panels disagree

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: SNCA
Protein: p.Glu83=
Coding: c.249G>A
MANE Select: NM_000345
dbSNP: rs1737224483
Type: single nucleotide variant
Location: chr4:89822303 (GRCh38)
Gene constraint: LOEUF 0.691 · pLI 0.80 (gnomAD)
Structure: AlphaFold pLDDT 74.29 · 185 PDB
Residue 83: a β-strand

Full SNCA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Parkinson Disease, Dominant

Similar variants

SNCA p.Glu83Gln Uncertain significance ★ ⚠ same residue
SNCA p.Ala53Glu Pathogenic ★★ ⚠ same condition
SNCA p.Ala53Thr Pathogenic ★★ ⚠ same condition
SNCA c.-219G>C Uncertain significance ★★ same condition
SNCA c.*2037T>C Uncertain significance ★★ same condition
SNCA p.Pro128Thr Uncertain significance ★★ ⚠ same condition
SNCA c.121+11C>T Benign/Likely benign ★★ same condition
SNCA c.*1287G>A Benign ★★ 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/snca-p-glu83 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown