Is PRRT2 p.Ala211fs (c.629dup) pathogenic?

PRRT2 p.Ala211fs (c.629dup) is classified Pathogenic in PRRT2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-06-11). Very rare (popmax 0.00181%, amr); Associated with PRRT2-Related Disorder.

What condition is associated with PRRT2 p.Ala211fs (c.629dup)?

PRRT2 p.Ala211fs (c.629dup) is associated with PRRT2-Related Disorder, infantile convulsions and choreoathetosis, seizures, benign familial infantile, 2 (ClinVar).

How common is PRRT2 p.Ala211fs (c.629dup) in the general population?

PRRT2 p.Ala211fs (c.629dup) is very rare (popmax 0.00181%, amr) (gnomAD).

PRRT2 p.Ala211fs

c.629dup · rs730882067 · VCV31171

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00181%, amr)

Conditions

PRRT2-Related Disorder

⚠ 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
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.79	GERP -2.2

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00181% Admixed American · 1/55,154 alleles

Filtering AF 0.000186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000122%

Overall 0.000891% 14/1,571,124 alleles · very rare exomes 14/1,429,412 · genomes 0/141,712 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00994%	10,061
Admixed Americangrpmax	0.00181%	55,154
Remaining individualsnot grpmax-eligible	0.00164%	60,874
European (non-Finnish)	0.000518%	193,118

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala211fs
Coding: c.629dup
MANE Select: NM_145239
dbSNP: rs730882067
Type: Duplication
Location: chr16:29813676 (GRCh38)

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

Disease context

Also linked: infantile convulsions and choreoathetosis seizures, benign familial infantile, 2 episodic kinesigenic dyskinesia episodic kinesigenic dyskinesia 1 PRRT2-associated paroxysmal movement disorder

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-ala211fs (accessed [today's date]).

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