Is PRRT2 p.Ile329Val (c.985A>G) pathogenic?

PRRT2 p.Ile329Val (c.985A>G) is classified Uncertain significance in PRRT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-08). AlphaMissense: likely benign (0.1386); No allele count reported in gnomAD v4.1 (AN 1,604,764); Associated with episodic kinesigenic dyskinesia.

What condition is associated with PRRT2 p.Ile329Val (c.985A>G)?

PRRT2 p.Ile329Val (c.985A>G) is associated with episodic kinesigenic dyskinesia (ClinVar).

How common is PRRT2 p.Ile329Val (c.985A>G) in the general population?

PRRT2 p.Ile329Val (c.985A>G) is no allele count reported in gnomAD v4.1 (AN 1,604,764) (gnomAD).

How is Paroxysmal kinesigenic dyskinesia inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about PRRT2 p.Ile329Val (c.985A>G)?

AlphaMissense predicts likely benign (score 0.1386) — an in-silico prediction, not a clinical call.

PRRT2 p.Ile329Val

c.985A>G · rs2142429495 · VCV1186731

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1386 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,604,764)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

episodic kinesigenic dyskinesia

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1386	likely benign
REVEL	0.251	benign-leaning
SaProt	LLR -7.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 0.71, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 709 bp · p 0.39 · regional, not allelic
Overall
CADD	21.2	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

No allele count reported in gnomAD v4.1 (AN 1,604,764). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PRRT2
Protein: p.Ile329Val
Coding: c.985A>G
MANE Select: NM_145239
dbSNP: rs2142429495
Type: single nucleotide variant
Location: chr16:29814438 (GRCh38)

Full PRRT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

episodic kinesigenic dyskinesia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Paroxysmal kinesigenic dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 1 000 000 (Worldwide)

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/prrt2-p-ile329val (accessed [today's date]).

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