Is PRRT2 p.Arg240Ter (c.718C>T) pathogenic?

PRRT2 p.Arg240Ter (c.718C>T) is classified Pathogenic in PRRT2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-04-23). Very rare (popmax 0.00269%, afr); Associated with episodic kinesigenic dyskinesia.

What condition is associated with PRRT2 p.Arg240Ter (c.718C>T)?

PRRT2 p.Arg240Ter (c.718C>T) is associated with episodic kinesigenic dyskinesia, infantile convulsions and choreoathetosis, seizures, benign familial infantile, 2 (ClinVar).

How common is PRRT2 p.Arg240Ter (c.718C>T) in the general population?

PRRT2 p.Arg240Ter (c.718C>T) is very rare (popmax 0.00269%, afr) (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.Arg240Ter

c.718C>T · rs387907126 · VCV31174

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00269%, afr)

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.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.8	GERP 0.12, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00269% African / African-American · 2/74,462 alleles

Filtering AF 0.000446% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000167%

Overall 0.000313% 5/1,599,774 alleles · very rare exomes 5/1,447,676 · genomes 0/152,098 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00353%	28,300
African / African-Americangrpmax	0.00269%	37,231
European (non-Finnish)	0.000171%	586,424

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg240Ter
Coding: c.718C>T
MANE Select: NM_145239
dbSNP: rs387907126
Type: single nucleotide variant
Location: chr16:29813772 (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-arg240ter (accessed [today's date]).

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