Is SNCA p.Val15Ala (c.44T>C) pathogenic?

SNCA p.Val15Ala (c.44T>C) is classified Conflicting classifications of pathogenicity in SNCA (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-06-12). AlphaMissense: likely pathogenic (0.601); Very rare (popmax 8.47e-05%, nfe); Associated with autosomal dominant Parkinson disease 1.

What condition is associated with SNCA p.Val15Ala (c.44T>C)?

SNCA p.Val15Ala (c.44T>C) is associated with autosomal dominant Parkinson disease 1 (ClinVar).

How common is SNCA p.Val15Ala (c.44T>C) in the general population?

SNCA p.Val15Ala (c.44T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Hereditary late-onset Parkinson disease inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about SNCA p.Val15Ala (c.44T>C)?

AlphaMissense predicts likely pathogenic (score 0.601) — an in-silico prediction, not a clinical call.

SNCA p.Val15Ala

c.44T>C · rs1739238968 · VCV871101

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.601 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal dominant Parkinson disease 1

Computational evidence

Protein change
AlphaMissense	0.601	likely pathogenic
REVEL	0.842	moderately pathogenic-leaning
SaProt	LLR -12.33	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 109 kb · p 0.025 · regional, not allelic
Overall
CADD	26.5	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,958 alleles

Overall 6.2e-05% 1/1,613,786 alleles · very rare exomes 0/1,461,810 · genomes 1/151,976 · 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.Val15Ala
Coding: c.44T>C
MANE Select: NM_000345
dbSNP: rs1739238968
Type: single nucleotide variant
Location: chr4:89835624 (GRCh38)
Gene constraint: LOEUF 0.691 · pLI 0.80 (gnomAD)
Structure: AlphaFold pLDDT 74.29 · 185 PDB

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

Disease context

autosomal dominant Parkinson disease 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary late-onset Parkinson disease (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

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-val15ala (accessed [today's date]).

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