Is PRRT2 p.Ser208Phe (c.623C>T) pathogenic?

PRRT2 p.Ser208Phe (c.623C>T) is classified Uncertain significance in PRRT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-09). AlphaMissense: likely benign (0.1336); Very rare (popmax 0.00275%, afr); Associated with episodic kinesigenic dyskinesia.

What condition is associated with PRRT2 p.Ser208Phe (c.623C>T)?

PRRT2 p.Ser208Phe (c.623C>T) is associated with episodic kinesigenic dyskinesia (ClinVar).

How common is PRRT2 p.Ser208Phe (c.623C>T) in the general population?

PRRT2 p.Ser208Phe (c.623C>T) is very rare (popmax 0.00275%, afr) (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.Ser208Phe (c.623C>T)?

AlphaMissense predicts likely benign (score 0.1336) — an in-silico prediction, not a clinical call.

PRRT2 p.Ser208Phe

c.623C>T · rs201409113 · VCV206698

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1336 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00275%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

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	0.1336	likely benign
REVEL	0.372	indeterminate
SaProt	LLR -9.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.44	GERP -0.1
Regional constraint	o/e 1.16	unconstrained · MANE · 785 bp · p 0.003 · regional, not allelic
Overall
CADD	17.16	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 0.00275% African / African-American · 2/72,844 alleles

Filtering AF 0.000646% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000498%

Overall 0.00104% 16/1,541,704 alleles · very rare exomes 15/1,390,550 · genomes 1/151,154 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00275%	36,422
European (non-Finnish)	0.00116%	86,408
South Asian	0.00113%	88,278

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.Ser208Phe
Coding: c.623C>T
MANE Select: NM_145239
dbSNP: rs201409113
Type: single nucleotide variant
Location: chr16:29813677 (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

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-ser208phe (accessed [today's date]).

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