Is PRRT2 p.Arg295Trp (c.883C>T) pathogenic?

PRRT2 p.Arg295Trp (c.883C>T) is classified Conflicting classifications of pathogenicity in PRRT2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-11-25). AlphaMissense: likely pathogenic (0.8845); Very rare (popmax 0.00331%, nfe); Associated with episodic kinesigenic dyskinesia.

What condition is associated with PRRT2 p.Arg295Trp (c.883C>T)?

PRRT2 p.Arg295Trp (c.883C>T) is associated with episodic kinesigenic dyskinesia (ClinVar).

How common is PRRT2 p.Arg295Trp (c.883C>T) in the general population?

PRRT2 p.Arg295Trp (c.883C>T) is very rare (popmax 0.00331%, nfe) (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.Arg295Trp (c.883C>T)?

AlphaMissense predicts likely pathogenic (score 0.8845) — an in-silico prediction, not a clinical call.

PRRT2 p.Arg295Trp

c.883C>T · rs200185554 · VCV846701

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.8845 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00331%, nfe)

Missense predictors

3/3 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	0.8845	likely pathogenic
REVEL	0.811	moderately pathogenic-leaning
SaProt	LLR -11.49	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.1	GERP 1.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 709 bp · p 0.39 · regional, not allelic
Overall
CADD	33.0	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 0.00331% European (non-Finnish) · 39/1,177,298 alleles

Filtering AF 0.00248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00218%

Overall 0.00256% 41/1,600,212 alleles · very rare exomes 39/1,448,012 · genomes 2/152,200 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00331%	30,187
East Asian	0.00223%	44,826
South Asian	0.00111%	90,320

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: PRRT2
Protein: p.Arg295Trp
Coding: c.883C>T
MANE Select: NM_145239
dbSNP: rs200185554
Type: single nucleotide variant
Location: chr16:29814336 (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-arg295trp (accessed [today's date]).

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