Is SNCA p.Val49= (c.147G>A) pathogenic?

SNCA p.Val49= (c.147G>A) is classified Likely benign in SNCA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-27). Ultra-rare (popmax 0.0153%, nfe); Associated with Lewy body dementia.

What condition is associated with SNCA p.Val49= (c.147G>A)?

SNCA p.Val49= (c.147G>A) is associated with Lewy body dementia, autosomal dominant Parkinson disease 1 (ClinVar).

How common is SNCA p.Val49= (c.147G>A) in the general population?

SNCA p.Val49= (c.147G>A) is ultra-rare (popmax 0.0153%, nfe) (gnomAD).

SNCA p.Val49=

c.147G>A · rs141859659 · VCV767542

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0153%, nfe)

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 1.5	GERP -3.5, phastCons 1
Overall
CADD	5.668	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0153% European (non-Finnish) · 181/1,179,398 alleles

Filtering AF 0.0135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.0131% 211/1,613,258 alleles · ultra-rare exomes 186/1,461,064 · genomes 25/152,194 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0153%	6,516
Admixed American	0.015%	6,666
Finnishnot grpmax-eligible	0.0141%	7,108
Remaining individualsnot grpmax-eligible	0.0112%	8,924
South Asian	0.00329%	30,351
African / African-American	0.00267%	37,500

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.Val49=
Coding: c.147G>A
MANE Select: NM_000345
dbSNP: rs141859659
Type: single nucleotide variant
Location: chr4:89828159 (GRCh38)
Gene constraint: LOEUF 0.691 · pLI 0.80 (gnomAD)
Structure: AlphaFold pLDDT 74.29 · 185 PDB
Residue 49: 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-val49 (accessed [today's date]).

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