Is PRRT2 p.Ala189Pro (c.565G>C) pathogenic?

PRRT2 p.Ala189Pro (c.565G>C) is classified Uncertain significance in PRRT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-23). AlphaMissense: likely benign (0.1653); Very rare (popmax 0.0011%, nfe); Associated with seizures, benign familial infantile, 2.

What condition is associated with PRRT2 p.Ala189Pro (c.565G>C)?

PRRT2 p.Ala189Pro (c.565G>C) is associated with seizures, benign familial infantile, 2, infantile convulsions and choreoathetosis, episodic kinesigenic dyskinesia (ClinVar).

How common is PRRT2 p.Ala189Pro (c.565G>C) in the general population?

PRRT2 p.Ala189Pro (c.565G>C) is very rare (popmax 0.0011%, nfe) (gnomAD).

How is Self-limited infantile epilepsy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about PRRT2 p.Ala189Pro (c.565G>C)?

AlphaMissense predicts likely benign (score 0.1653) — an in-silico prediction, not a clinical call.

PRRT2 p.Ala189Pro

c.565G>C · VCV3580044

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1653 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

seizures, benign familial infantile, 2

⚠ 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	0.1653	likely benign
REVEL	0.182	moderately benign-leaning
SaProt	LLR -5.59	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.6	GERP 1.2, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 785 bp · p 0.003 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% European (non-Finnish) · 13/1,179,690 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000806% 13/1,613,222 alleles · very rare exomes 12/1,461,070 · genomes 1/152,152 · joint denominator

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.Ala189Pro
Coding: c.565G>C
MANE Select: NM_145239
Type: single nucleotide variant
Location: chr16:29813619 (GRCh38)

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

Disease context

seizures, benign familial infantile, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: infantile convulsions and choreoathetosis episodic kinesigenic dyskinesia episodic kinesigenic dyskinesia 1

For Self-limited infantile epilepsy (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

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-ala189pro (accessed [today's date]).

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