Is PRRT2 p.Gly337Asp (c.1010G>A) pathogenic?

PRRT2 p.Gly337Asp (c.1010G>A) is classified Uncertain significance in PRRT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-24). AlphaMissense: likely pathogenic (0.9782); Absent from gnomAD v4.1; Associated with episodic kinesigenic dyskinesia.

What condition is associated with PRRT2 p.Gly337Asp (c.1010G>A)?

PRRT2 p.Gly337Asp (c.1010G>A) is associated with episodic kinesigenic dyskinesia (ClinVar).

How common is PRRT2 p.Gly337Asp (c.1010G>A) in the general population?

PRRT2 p.Gly337Asp (c.1010G>A) is absent from gnomAD v4.1 (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.Gly337Asp (c.1010G>A)?

AlphaMissense predicts likely pathogenic (score 0.9782) — an in-silico prediction, not a clinical call.

PRRT2 p.Gly337Asp

c.1010G>A · rs1900144446 · VCV941395

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9782 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

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	0.9782	likely pathogenic
REVEL	0.367	indeterminate
SaProt	LLR -7.90	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP -3.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 709 bp · p 0.39 · regional, not allelic
Overall
CADD	26.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRRT2
Protein: p.Gly337Asp
Coding: c.1010G>A
MANE Select: NM_145239
dbSNP: rs1900144446
Type: single nucleotide variant
Location: chr16:29814463 (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-gly337asp (accessed [today's date]).

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