Is PRRT2 p.Glu127= (c.381G>A) pathogenic?

PRRT2 p.Glu127= (c.381G>A) is classified Likely benign in PRRT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-03). Ultra-rare (popmax 0.0231%, sas); Associated with episodic kinesigenic dyskinesia.

What condition is associated with PRRT2 p.Glu127= (c.381G>A)?

PRRT2 p.Glu127= (c.381G>A) is associated with episodic kinesigenic dyskinesia (ClinVar).

How common is PRRT2 p.Glu127= (c.381G>A) in the general population?

PRRT2 p.Glu127= (c.381G>A) is ultra-rare (popmax 0.0231%, sas) (gnomAD).

How is Paroxysmal kinesigenic dyskinesia inherited?

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

PRRT2 p.Glu127=

c.381G>A · rs747609927 · VCV787714

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, sas)

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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.77	GERP -2.2, phastCons 0.011
Overall
CADD	1.715	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0231% South Asian · 21/91,082 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.00136% 22/1,614,106 alleles · ultra-rare exomes 21/1,461,834 · genomes 1/152,272 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0231%	4,337
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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.Glu127=
Coding: c.381G>A
MANE Select: NM_145239
dbSNP: rs747609927
Type: single nucleotide variant
Location: chr16:29813435 (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-glu127 (accessed [today's date]).

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