Is PRRT2 p.Arg145Gln (c.434G>A) pathogenic?

PRRT2 p.Arg145Gln (c.434G>A) is classified Conflicting classifications of pathogenicity in PRRT2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0523); Ultra-rare (popmax 0.015%, amr); Associated with episodic kinesigenic dyskinesia.

What condition is associated with PRRT2 p.Arg145Gln (c.434G>A)?

PRRT2 p.Arg145Gln (c.434G>A) is associated with episodic kinesigenic dyskinesia, infantile convulsions and choreoathetosis, seizures, benign familial infantile, 2 (ClinVar).

How common is PRRT2 p.Arg145Gln (c.434G>A) in the general population?

PRRT2 p.Arg145Gln (c.434G>A) is ultra-rare (popmax 0.015%, amr) (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.Arg145Gln (c.434G>A)?

AlphaMissense predicts likely benign (score 0.0523) — an in-silico prediction, not a clinical call.

PRRT2 p.Arg145Gln

c.434G>A · rs200877676 · VCV568591

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0523 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

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	0.0523	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -3.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.7	GERP 0.078, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 785 bp · p 0.003 · regional, not allelic
Overall
CADD	16.13	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 0.015% Admixed American · 9/59,966 alleles

Filtering AF 0.00774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.00143% 23/1,613,258 alleles · ultra-rare exomes 12/1,461,440 · genomes 11/151,818 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,663
Remaining individualsnot grpmax-eligible	0.008%	12,494
African / African-American	0.00401%	24,933
East Asian	0.00223%	44,856
European (non-Finnish)	0.000424%	235,929

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.Arg145Gln
Coding: c.434G>A
MANE Select: NM_145239
dbSNP: rs200877676
Type: single nucleotide variant
Location: chr16:29813488 (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

Also linked: infantile convulsions and choreoathetosis seizures, benign familial infantile, 2 episodic kinesigenic dyskinesia 1

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-arg145gln (accessed [today's date]).

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