Is PRRT2 p.Glu23Lys (c.67G>A) pathogenic?

PRRT2 p.Glu23Lys (c.67G>A) is classified Conflicting classifications of pathogenicity in PRRT2 (ClinVar, Conflicting submitters, 13 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.0771); Rare (popmax 0.248%, nfe); Associated with episodic kinesigenic dyskinesia 1.

What condition is associated with PRRT2 p.Glu23Lys (c.67G>A)?

PRRT2 p.Glu23Lys (c.67G>A) is associated with episodic kinesigenic dyskinesia 1, infantile convulsions and choreoathetosis, seizures, benign familial infantile, 2 (ClinVar).

How common is PRRT2 p.Glu23Lys (c.67G>A) in the general population?

PRRT2 p.Glu23Lys (c.67G>A) is rare (popmax 0.248%, 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.Glu23Lys (c.67G>A)?

AlphaMissense predicts likely benign (score 0.0771) — an in-silico prediction, not a clinical call.

PRRT2 p.Glu23Lys

c.67G>A · rs140383655 · VCV130039

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 13 submitters

AlphaMissense

likely benign

0.0771 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.248%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

episodic kinesigenic dyskinesia 1

⚠ 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	0.0771	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -8.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.94	GERP -2.5, phastCons 0.69
Regional constraint	o/e 1.16	unconstrained · MANE · 785 bp · p 0.003 · regional, not allelic
Overall
CADD	13.9	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 0.248% European (non-Finnish) · 2,931/1,179,924 alleles

Filtering AF 0.241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.238%

Overall 0.199% 3,205/1,613,926 alleles · rare exomes 3,035/1,461,668 · genomes 170/152,258 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.248%	403
Remaining individualsnot grpmax-eligible	0.206%	484
Admixed American	0.14%	714
African / African-American	0.044%	2,273
Finnishnot grpmax-eligible	0.0344%	2,908
South Asian	0.00659%	15,181

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.Glu23Lys
Coding: c.67G>A
MANE Select: NM_145239
dbSNP: rs140383655
Type: single nucleotide variant
Location: chr16:29813121 (GRCh38)

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

Disease context

episodic kinesigenic dyskinesia 1 — 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

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-glu23lys (accessed [today's date]).

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