Is PRRT2 p.Ala291Thr (c.871G>A) pathogenic?

PRRT2 p.Ala291Thr (c.871G>A) is classified Uncertain significance in PRRT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-22). AlphaMissense: likely pathogenic (0.9322); Absent from gnomAD v4.1; Associated with episodic kinesigenic dyskinesia.

What condition is associated with PRRT2 p.Ala291Thr (c.871G>A)?

PRRT2 p.Ala291Thr (c.871G>A) is associated with episodic kinesigenic dyskinesia (ClinVar).

How common is PRRT2 p.Ala291Thr (c.871G>A) in the general population?

PRRT2 p.Ala291Thr (c.871G>A) 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.

What do computational predictors say about PRRT2 p.Ala291Thr (c.871G>A)?

AlphaMissense predicts likely pathogenic (score 0.9322) — an in-silico prediction, not a clinical call.

PRRT2 p.Ala291Thr

c.871G>A · rs1596893141 · VCV639782

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9322 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

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	0.9322	likely pathogenic
REVEL	0.63	indeterminate
SaProt	LLR -8.92	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.9	GERP -3.3, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 84 bp · p 0.0007 · regional, not allelic
Overall
CADD	29.7	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

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.Ala291Thr
Coding: c.871G>A
MANE Select: NM_145239
dbSNP: rs1596893141
Type: single nucleotide variant
Location: chr16:29813925 (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-ala291thr (accessed [today's date]).

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