Is SNCA p.Val52= (c.156G>T) pathogenic?

SNCA p.Val52= (c.156G>T) is classified Likely benign in SNCA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-09). Ultra-rare (popmax 0.0547%, afr); Associated with Lewy body dementia.

What condition is associated with SNCA p.Val52= (c.156G>T)?

SNCA p.Val52= (c.156G>T) is associated with Lewy body dementia, autosomal dominant Parkinson disease 1 (ClinVar).

How common is SNCA p.Val52= (c.156G>T) in the general population?

SNCA p.Val52= (c.156G>T) is ultra-rare (popmax 0.0547%, afr) (gnomAD).

SNCA p.Val52=

c.156G>T · rs148108612 · VCV772345

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0547%, afr)

Conditions

Lewy body dementia

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 1	GERP 2, phastCons 1
Overall
CADD	7.547	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0547% African / African-American · 41/74,934 alleles

Filtering AF 0.0414% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0368%

Overall 0.00254% 41/1,612,724 alleles · ultra-rare exomes 14/1,460,614 · genomes 27/152,110 · 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: SNCA
Protein: p.Val52=
Coding: c.156G>T
MANE Select: NM_000345
dbSNP: rs148108612
Type: single nucleotide variant
Location: chr4:89828150 (GRCh38)
Gene constraint: LOEUF 0.691 · pLI 0.80 (gnomAD)
Structure: AlphaFold pLDDT 74.29 · 185 PDB
Residue 52: a β-strand; the '4 x 11 aa tandem repeats of [egs]-k-t-k-[eq]-[gq]-v-x(4)' region

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

Disease context

Lewy body dementia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal dominant Parkinson disease 1

Similar variants

SNCA p.Ala53Glu Pathogenic ★★ ⚠ same condition
SNCA p.Ala53Thr Pathogenic ★★ ⚠ same condition
SNCA p.His50Gln Uncertain significance ★★ ⚠ same condition
SNCA p.Pro117Thr Uncertain significance ★★ ⚠ same condition
SNCA p.Pro128Thr Uncertain significance ★★ ⚠ same condition
SNCA c.121+11C>T Benign/Likely benign ★★ same condition
SNCA c.391-16A>G Likely benign ★★ same condition
SNCA c.*139T>G Benign/Likely 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-val52 (accessed [today's date]).

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