Is PRRT2 p.Val303Met (c.907G>A) pathogenic?

PRRT2 p.Val303Met (c.907G>A) is classified Uncertain significance in PRRT2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-21). AlphaMissense: likely benign (0.2943); Ultra-rare (popmax 0.0169%, mid); Associated with episodic kinesigenic dyskinesia.

What condition is associated with PRRT2 p.Val303Met (c.907G>A)?

PRRT2 p.Val303Met (c.907G>A) is associated with episodic kinesigenic dyskinesia (ClinVar).

How common is PRRT2 p.Val303Met (c.907G>A) in the general population?

PRRT2 p.Val303Met (c.907G>A) is ultra-rare (popmax 0.0169%, mid) (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.Val303Met (c.907G>A)?

AlphaMissense predicts likely benign (score 0.2943) — an in-silico prediction, not a clinical call.

PRRT2 p.Val303Met

c.907G>A · rs774683543 · VCV838983

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2943 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0169%, mid)

Missense predictors

0/2 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	0.2943	likely benign
REVEL	0.336	indeterminate
SaProt	LLR -8.69	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.9	GERP -3.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 709 bp · p 0.39 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0169% Middle Eastern · 1/5,910 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000901%

Overall 0.00137% 22/1,607,850 alleles · ultra-rare exomes 22/1,455,640 · genomes 0/152,210 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0169%	5,910
European (non-Finnish)	0.0017%	58,946
South Asian	0.0011%	90,798

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.Val303Met
Coding: c.907G>A
MANE Select: NM_145239
dbSNP: rs774683543
Type: single nucleotide variant
Location: chr16:29814360 (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-val303met (accessed [today's date]).

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