Is PRRT2 c.1012+2T>C pathogenic?

PRRT2 c.1012+2T>C is classified Uncertain significance in PRRT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-02). Absent from gnomAD v4.1; Associated with episodic kinesigenic dyskinesia.

What condition is associated with PRRT2 c.1012+2T>C?

PRRT2 c.1012+2T>C is associated with episodic kinesigenic dyskinesia (ClinVar).

How common is PRRT2 c.1012+2T>C in the general population?

PRRT2 c.1012+2T>C is absent from gnomAD v4.1 (gnomAD).

How is Paroxysmal kinesigenic dyskinesia inherited?

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

PRRT2 c.1012+2T>C

rs2543339500 · VCV2982331

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.55	loss · gain 0.04 · independent
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Non-coding constraint	Z 4.12	1 kb window · o/e 0.75 · regional · uncalibrated
Overall
CADD	24.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRRT2
Coding: c.1012+2T>C
MANE Select: NM_145239
dbSNP: rs2543339500
Type: single nucleotide variant
Location: chr16:29814467 (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-c-1012-plus-2t-c (accessed [today's date]).

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