Is PRRT2 p.Glu94Ter (c.280G>T) pathogenic?

PRRT2 p.Glu94Ter (c.280G>T) is classified Pathogenic/Likely pathogenic in PRRT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-01). Absent from gnomAD v4.1; Associated with PRRT2-Related Disorder.

What condition is associated with PRRT2 p.Glu94Ter (c.280G>T)?

PRRT2 p.Glu94Ter (c.280G>T) is associated with PRRT2-Related Disorder, episodic kinesigenic dyskinesia (ClinVar).

How common is PRRT2 p.Glu94Ter (c.280G>T) in the general population?

PRRT2 p.Glu94Ter (c.280G>T) is absent from gnomAD v4.1 (gnomAD).

PRRT2 p.Glu94Ter

c.280G>T · VCV4716489

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

PRRT2-Related Disorder

⚠ 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 3.4	GERP -2, phastCons 1
Overall
CADD	34.0	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

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
Protein: p.Glu94Ter
Coding: c.280G>T
MANE Select: NM_145239
Type: single nucleotide variant
Location: chr16:29813334 (GRCh38)

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

Disease context

Also linked: episodic kinesigenic dyskinesia

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-glu94ter (accessed [today's date]).

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