Is PRRT2 p.Ser208fs (c.621dup) pathogenic?

PRRT2 p.Ser208fs (c.621dup) is classified Pathogenic in PRRT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-03). Very rare (popmax 0.0017%, amr).

How common is PRRT2 p.Ser208fs (c.621dup) in the general population?

PRRT2 p.Ser208fs (c.621dup) is very rare (popmax 0.0017%, amr) (gnomAD).

PRRT2 p.Ser208fs

c.621dup · rs768603598 · VCV1323500

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0017%, amr)

⚠ 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 3.8	GERP 1.1, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0017% Admixed American · 1/58,938 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000187% 3/1,606,964 alleles · very rare exomes 3/1,454,846 · genomes 0/152,118 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0017%	58,938
European (non-Finnish)	0.00017%	588,291

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.Ser208fs
Coding: c.621dup
MANE Select: NM_145239
dbSNP: rs768603598
Type: Duplication
Location: chr16:29813668 (GRCh38)

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

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-ser208fs (accessed [today's date]).

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