Is PRRT2 p.Glu164Lys (c.490G>A) pathogenic?

PRRT2 p.Glu164Lys (c.490G>A) is classified Conflicting classifications of pathogenicity in PRRT2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-02-20). AlphaMissense: likely benign (0.0866); Very rare (popmax 0.00401%, afr); Associated with episodic kinesigenic dyskinesia.

What condition is associated with PRRT2 p.Glu164Lys (c.490G>A)?

PRRT2 p.Glu164Lys (c.490G>A) is associated with episodic kinesigenic dyskinesia (ClinVar).

How common is PRRT2 p.Glu164Lys (c.490G>A) in the general population?

PRRT2 p.Glu164Lys (c.490G>A) is very rare (popmax 0.00401%, afr) (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.Glu164Lys (c.490G>A)?

AlphaMissense predicts likely benign (score 0.0866) — an in-silico prediction, not a clinical call.

PRRT2 p.Glu164Lys

c.490G>A · rs752707110 · VCV1024078

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0866 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

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	0.0866	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -6.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.8	GERP 1.2, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 785 bp · p 0.003 · regional, not allelic
Overall
CADD	21.6	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 0.00401% African / African-American · 3/74,896 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00031% 5/1,613,718 alleles · very rare exomes 4/1,461,586 · genomes 1/152,132 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,965
Admixed American	0.00167%	59,996
South Asian	0.0011%	91,084

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.Glu164Lys
Coding: c.490G>A
MANE Select: NM_145239
dbSNP: rs752707110
Type: single nucleotide variant
Location: chr16:29813544 (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-glu164lys (accessed [today's date]).

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