Is PRRT2 p.Val338Ala (c.1013T>C) pathogenic?

PRRT2 p.Val338Ala (c.1013T>C) is classified Conflicting classifications of pathogenicity in PRRT2 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-06-10). AlphaMissense: ambiguous (0.4078); Ultra-rare (popmax 0.0357%, nfe); Associated with episodic kinesigenic dyskinesia.

What condition is associated with PRRT2 p.Val338Ala (c.1013T>C)?

PRRT2 p.Val338Ala (c.1013T>C) is associated with episodic kinesigenic dyskinesia (ClinVar).

How common is PRRT2 p.Val338Ala (c.1013T>C) in the general population?

PRRT2 p.Val338Ala (c.1013T>C) is ultra-rare (popmax 0.0357%, nfe) (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.Val338Ala (c.1013T>C)?

AlphaMissense predicts ambiguous (score 0.4078) — an in-silico prediction, not a clinical call.

PRRT2 p.Val338Ala

c.1013T>C · rs144540943 · VCV197379

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

ambiguous

0.4078 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0357%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense 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	0.4078	ambiguous
REVEL	0.161	moderately benign-leaning
SaProt	LLR -8.24	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.8	GERP 1.2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 709 bp · p 0.39 · regional, not allelic
Overall
CADD	21.7	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

Grpmax group 0.0357% European (non-Finnish) · 417/1,168,830 alleles

Filtering AF 0.0328% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0317%

Overall 0.0284% 453/1,594,682 alleles · ultra-rare exomes 420/1,445,670 · genomes 33/149,012 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0357%	2,803
Remaining individualsnot grpmax-eligible	0.0228%	4,380
Admixed American	0.0186%	5,375
African / African-American	0.0109%	9,199
Finnishnot grpmax-eligible	0.0032%	31,290
South Asian	0.00111%	90,432

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.Val338Ala
Coding: c.1013T>C
MANE Select: NM_145239
dbSNP: rs144540943
Type: single nucleotide variant
Location: chr16:29814628 (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-val338ala (accessed [today's date]).

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