Is PRRT2 p.Arg308His (c.923G>A) pathogenic?

PRRT2 p.Arg308His (c.923G>A) is classified Conflicting classifications of pathogenicity in PRRT2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-04-29). AlphaMissense: likely pathogenic (0.732); Ultra-rare (popmax 0.0151%, amr); Associated with Inborn genetic diseases.

What condition is associated with PRRT2 p.Arg308His (c.923G>A)?

PRRT2 p.Arg308His (c.923G>A) is associated with Inborn genetic diseases, episodic kinesigenic dyskinesia (ClinVar).

How common is PRRT2 p.Arg308His (c.923G>A) in the general population?

PRRT2 p.Arg308His (c.923G>A) is ultra-rare (popmax 0.0151%, amr) (gnomAD).

What do computational predictors say about PRRT2 p.Arg308His (c.923G>A)?

AlphaMissense predicts likely pathogenic (score 0.732) — an in-silico prediction, not a clinical call.

PRRT2 p.Arg308His

c.923G>A · rs989894169 · VCV404416

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.732 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0151%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

⚠ 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	0.732	likely pathogenic
REVEL	0.735	pathogenic-leaning
SaProt	LLR -11.75	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 709 bp · p 0.39 · regional, not allelic
Overall
CADD	34.0	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 0.0151% Admixed American · 9/59,752 alleles

Filtering AF 0.00776% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00581%

Overall 0.00118% 19/1,610,168 alleles · ultra-rare exomes 17/1,458,068 · genomes 2/152,100 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0151%	6,639
Remaining individualsnot grpmax-eligible	0.00321%	31,182
Finnishnot grpmax-eligible	0.00162%	61,894
European (non-Finnish)	0.000594%	168,453

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.Arg308His
Coding: c.923G>A
MANE Select: NM_145239
dbSNP: rs989894169
Type: single nucleotide variant
Location: chr16:29814376 (GRCh38)

Full PRRT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: episodic kinesigenic dyskinesia

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-arg308his (accessed [today's date]).

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