Is PRRT2 p.Pro168= (c.504T>G) pathogenic?

PRRT2 p.Pro168= (c.504T>G) is classified Likely benign in PRRT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-01). Ultra-rare (popmax 0.0109%, nfe).

How common is PRRT2 p.Pro168= (c.504T>G) in the general population?

PRRT2 p.Pro168= (c.504T>G) is ultra-rare (popmax 0.0109%, nfe) (gnomAD).

PRRT2 p.Pro168=

c.504T>G · rs2543334028 · VCV2646370

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0109%, nfe)

⚠ 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.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.31	GERP -0.92, phastCons 0.12
Overall
CADD	4.394	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0109% European (non-Finnish) · 128/1,177,948 alleles

Filtering AF 0.00929% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00873%

Overall 0.00832% 134/1,610,804 alleles · ultra-rare exomes 134/1,459,710 · genomes 0/151,094 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0109%	9,203
Remaining individualsnot grpmax-eligible	0.00641%	15,602
East Asian	0.00447%	22,385

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.Pro168=
Coding: c.504T>G
MANE Select: NM_145239
dbSNP: rs2543334028
Type: single nucleotide variant
Location: chr16:29813558 (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-pro168 (accessed [today's date]).

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