Is PRRT2 p.Asp147His (c.439G>C) pathogenic?

PRRT2 p.Asp147His (c.439G>C) is classified Benign/Likely benign in PRRT2 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.1255); Low-frequency (popmax 1.18%, eas); Associated with episodic kinesigenic dyskinesia.

What condition is associated with PRRT2 p.Asp147His (c.439G>C)?

PRRT2 p.Asp147His (c.439G>C) is associated with episodic kinesigenic dyskinesia, infantile convulsions and choreoathetosis, seizures, benign familial infantile, 2 (ClinVar).

How common is PRRT2 p.Asp147His (c.439G>C) in the general population?

PRRT2 p.Asp147His (c.439G>C) is low-frequency (popmax 1.18%, 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.Asp147His (c.439G>C)?

AlphaMissense predicts likely benign (score 0.1255) — an in-silico prediction, not a clinical call.

PRRT2 p.Asp147His

c.439G>C · rs79568162 · VCV138813

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.1255 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.18%, 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	0.1255	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -9.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.2	GERP 1.2, phastCons 0.99
Regional constraint	o/e 1.16	unconstrained · MANE · 785 bp · p 0.003 · regional, not allelic
Overall
CADD	13.67	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 1.18% East Asian · 529/44,870 alleles

Filtering AF 1.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.06%

Overall 0.0438% 707/1,613,684 alleles · low-frequency exomes 626/1,461,478 · genomes 81/152,206 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.18%	85
Remaining individualsnot grpmax-eligible	0.245%	408
African / African-American	0.0133%	7,499
Admixed American	0.00167%	60,002
European (non-Finnish)	0.0011%	90,749
South Asian	0.0011%	91,084

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.Asp147His
Coding: c.439G>C
MANE Select: NM_145239
dbSNP: rs79568162
Type: single nucleotide variant
Location: chr16:29813493 (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

Also linked: infantile convulsions and choreoathetosis seizures, benign familial infantile, 2 episodic kinesigenic dyskinesia 1

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-asp147his (accessed [today's date]).

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