Is PRRT2 p.Pro144Leu (c.431C>T) pathogenic?

PRRT2 p.Pro144Leu (c.431C>T) is classified Conflicting classifications of pathogenicity in PRRT2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-25). AlphaMissense: likely benign (0.0781); Very rare (popmax 0.0022%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PRRT2 p.Pro144Leu (c.431C>T)?

PRRT2 p.Pro144Leu (c.431C>T) is associated with Inborn genetic diseases, episodic kinesigenic dyskinesia (ClinVar).

How common is PRRT2 p.Pro144Leu (c.431C>T) in the general population?

PRRT2 p.Pro144Leu (c.431C>T) is very rare (popmax 0.0022%, nfe) (gnomAD).

What do computational predictors say about PRRT2 p.Pro144Leu (c.431C>T)?

AlphaMissense predicts likely benign (score 0.0781) — an in-silico prediction, not a clinical call.

PRRT2 p.Pro144Leu

c.431C>T · rs1317648011 · VCV451350

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0781 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, nfe)

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	0.0781	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -7.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.2	GERP -0.045, phastCons 0.11
Regional constraint	o/e 1.16	unconstrained · MANE · 785 bp · p 0.003 · regional, not allelic
Overall
CADD	15.01	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 0.0022% European (non-Finnish) · 26/1,179,764 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00167% 27/1,613,670 alleles · very rare exomes 26/1,461,522 · genomes 1/152,148 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0022%	45,376
Remaining individualsnot grpmax-eligible	0.0016%	62,456

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.Pro144Leu
Coding: c.431C>T
MANE Select: NM_145239
dbSNP: rs1317648011
Type: single nucleotide variant
Location: chr16:29813485 (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-pro144leu (accessed [today's date]).

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