Is PRRT2 p.Arg145Trp (c.433C>T) pathogenic?

PRRT2 p.Arg145Trp (c.433C>T) is classified Conflicting classifications of pathogenicity in PRRT2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-02-03). AlphaMissense: likely benign (0.1038); Very rare (popmax 0.00892%, eas); Associated with Inborn genetic diseases.

What condition is associated with PRRT2 p.Arg145Trp (c.433C>T)?

PRRT2 p.Arg145Trp (c.433C>T) is associated with Inborn genetic diseases, episodic kinesigenic dyskinesia (ClinVar).

How common is PRRT2 p.Arg145Trp (c.433C>T) in the general population?

PRRT2 p.Arg145Trp (c.433C>T) is very rare (popmax 0.00892%, eas) (gnomAD).

What do computational predictors say about PRRT2 p.Arg145Trp (c.433C>T)?

AlphaMissense predicts likely benign (score 0.1038) — an in-silico prediction, not a clinical call.

PRRT2 p.Arg145Trp

c.433C>T · rs574304021 · VCV641115

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1038 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Missense predictors

0/3 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	0.1038	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -9.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.5	GERP 1.1, phastCons 0.96
Regional constraint	o/e 1.16	unconstrained · MANE · 785 bp · p 0.003 · regional, not allelic
Overall
CADD	23.4	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 0.00892% East Asian · 4/44,866 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.0013% 21/1,613,720 alleles · very rare exomes 14/1,461,424 · genomes 7/152,296 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,216
Admixed American	0.00333%	30,008
Remaining individualsnot grpmax-eligible	0.0016%	62,474
Finnishnot grpmax-eligible	0.00156%	63,980
European (non-Finnish)	0.0011%	90,747

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.Arg145Trp
Coding: c.433C>T
MANE Select: NM_145239
dbSNP: rs574304021
Type: single nucleotide variant
Location: chr16:29813487 (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-arg145trp (accessed [today's date]).

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