Is SNCAIP p.Pro130Ser (c.388C>T) pathogenic?

SNCAIP p.Pro130Ser (c.388C>T) is classified Uncertain significance in SNCAIP (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.0652); Ultra-rare (popmax 0.0201%, eas); Associated with Parkinson Disease, Dominant/Recessive.

What condition is associated with SNCAIP p.Pro130Ser (c.388C>T)?

SNCAIP p.Pro130Ser (c.388C>T) is associated with Parkinson Disease, Dominant/Recessive (ClinVar).

How common is SNCAIP p.Pro130Ser (c.388C>T) in the general population?

SNCAIP p.Pro130Ser (c.388C>T) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

What do computational predictors say about SNCAIP p.Pro130Ser (c.388C>T)?

AlphaMissense predicts likely benign (score 0.0652) — an in-silico prediction, not a clinical call.

SNCAIP p.Pro130Ser

c.388C>T · rs1776726284 · VCV904473

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0652 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Parkinson Disease, Dominant/Recessive

Computational evidence

Protein change
AlphaMissense	0.0652	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -5.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.3, phastCons 0.86
Regional constraint	o/e 0.89	unconstrained · MANE · 72 kb · p 0.00024 · regional, not allelic
Overall
CADD	11.43	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0201% East Asian · 9/44,846 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0078%

Overall 0.000558% 9/1,614,128 alleles · ultra-rare exomes 9/1,461,832 · genomes 0/152,296 · 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: SNCAIP
Protein: p.Pro130Ser
Coding: c.388C>T
MANE Select: NM_005460
dbSNP: rs1776726284
Type: single nucleotide variant
Location: chr5:122423125 (GRCh38)
Gene constraint: LOEUF 0.636 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.98 · 1 PDB
Residue 130: the 'disordered' region

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

Disease context

Parkinson Disease, Dominant/Recessive

Similar variants

SNCAIP p.Ala363Thr Uncertain significance ★★ ⚠ same condition
SNCAIP p.Glu237Lys Uncertain significance ★★ ⚠ same condition
SNCAIP p.Leu148= Uncertain significance ★★ same condition
SNCAIP p.Ser912Arg Uncertain significance ★★ ⚠ same condition
SNCAIP c.*103C>T Likely benign ★★ same condition
SNCAIP c.*46T>G Likely benign ★★ same condition
SNCAIP c.*70C>G Benign/Likely benign ★★ same condition
SNCAIP p.Arg621Cys 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/sncaip-p-pro130ser (accessed [today's date]).

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