Is PRRT2 p.Gln307His (c.921G>C) pathogenic?

PRRT2 p.Gln307His (c.921G>C) is classified Uncertain significance in PRRT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-01). AlphaMissense: ambiguous (0.3995); Very rare (popmax 0.00483%, nfe); Associated with episodic kinesigenic dyskinesia.

What condition is associated with PRRT2 p.Gln307His (c.921G>C)?

PRRT2 p.Gln307His (c.921G>C) is associated with episodic kinesigenic dyskinesia (ClinVar).

How common is PRRT2 p.Gln307His (c.921G>C) in the general population?

PRRT2 p.Gln307His (c.921G>C) is very rare (popmax 0.00483%, 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.Gln307His (c.921G>C)?

AlphaMissense predicts ambiguous (score 0.3995) — an in-silico prediction, not a clinical call.

PRRT2 p.Gln307His

c.921G>C · rs376602453 · VCV1433481

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3995 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00483%, nfe)

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	0.3995	ambiguous
REVEL	0.4	indeterminate
SaProt	LLR -9.78	tolerated
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.1	GERP 0.59, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 709 bp · p 0.39 · regional, not allelic
Overall
CADD	20.2	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 0.00483% European (non-Finnish) · 57/1,179,156 alleles

Filtering AF 0.00378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00345%

Overall 0.0036% 58/1,610,158 alleles · very rare exomes 58/1,457,898 · genomes 0/152,260 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00483%	20,687
Remaining individualsnot grpmax-eligible	0.0016%	62,380

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.Gln307His
Coding: c.921G>C
MANE Select: NM_145239
dbSNP: rs376602453
Type: single nucleotide variant
Location: chr16:29814374 (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-gln307his (accessed [today's date]).

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