Is PRRT2 p.Pro18Thr (c.52C>A) pathogenic?

PRRT2 p.Pro18Thr (c.52C>A) is classified Uncertain significance in PRRT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-27). AlphaMissense: likely benign (0.0683); Ultra-rare (popmax 0.0176%, sas); Associated with Inborn genetic diseases.

What condition is associated with PRRT2 p.Pro18Thr (c.52C>A)?

PRRT2 p.Pro18Thr (c.52C>A) is associated with Inborn genetic diseases, episodic kinesigenic dyskinesia (ClinVar).

How common is PRRT2 p.Pro18Thr (c.52C>A) in the general population?

PRRT2 p.Pro18Thr (c.52C>A) is ultra-rare (popmax 0.0176%, sas) (gnomAD).

What do computational predictors say about PRRT2 p.Pro18Thr (c.52C>A)?

AlphaMissense predicts likely benign (score 0.0683) — an in-silico prediction, not a clinical call.

PRRT2 p.Pro18Thr

c.52C>A · rs771505810 · VCV1746689

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0683 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, sas)

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	0.0683	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -7.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.34	GERP 1.4, phastCons 0.98
Regional constraint	o/e 1.16	unconstrained · MANE · 785 bp · p 0.003 · regional, not allelic
Overall
CADD	12.89	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 0.0176% South Asian · 16/91,072 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.00118% 19/1,613,670 alleles · ultra-rare exomes 16/1,461,410 · genomes 3/152,260 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0176%	5,692
Remaining individualsnot grpmax-eligible	0.0032%	31,240
East Asian	0.00223%	44,866

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.Pro18Thr
Coding: c.52C>A
MANE Select: NM_145239
dbSNP: rs771505810
Type: single nucleotide variant
Location: chr16:29813106 (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-pro18thr (accessed [today's date]).

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