Is PRRT2 p.Ala214Pro (c.640G>C) pathogenic?

PRRT2 p.Ala214Pro (c.640G>C) is classified Conflicting classifications of pathogenicity in PRRT2 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-03-01). AlphaMissense: likely benign (0.2247); Rare (popmax 0.361%, eas); Associated with episodic kinesigenic dyskinesia.

What condition is associated with PRRT2 p.Ala214Pro (c.640G>C)?

PRRT2 p.Ala214Pro (c.640G>C) is associated with episodic kinesigenic dyskinesia (ClinVar).

How common is PRRT2 p.Ala214Pro (c.640G>C) in the general population?

PRRT2 p.Ala214Pro (c.640G>C) is rare (popmax 0.361%, eas) (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.Ala214Pro (c.640G>C)?

AlphaMissense predicts likely benign (score 0.2247) — an in-silico prediction, not a clinical call.

PRRT2 p.Ala214Pro

c.640G>C · rs745594874 · VCV206687

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.2247 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.361%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

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	0.2247	likely benign
REVEL	0.211	benign-leaning
SaProt	LLR -7.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.2, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 785 bp · p 0.003 · regional, not allelic
Overall
CADD	25.3	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 0.361% East Asian · 153/42,416 alleles

Filtering AF 0.314% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.296%

Overall 0.0812% 1,223/1,505,356 alleles · rare exomes 1,087/1,355,752 · genomes 136/149,604 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.361%	277
South Asian	0.32%	313
African / African-American	0.122%	818
Remaining individualsnot grpmax-eligible	0.105%	952
Middle Eastern	0.07%	1,428
European (non-Finnish)	0.056%	1,786
Ashkenazi Jewishnot grpmax-eligible	0.0419%	2,389
Admixed American	0.0414%	2,414
Finnishnot grpmax-eligible	0.00827%	12,093

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.Ala214Pro
Coding: c.640G>C
MANE Select: NM_145239
dbSNP: rs745594874
Type: single nucleotide variant
Location: chr16:29813694 (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-ala214pro (accessed [today's date]).

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