Is PRRT2 p.Leu251= (c.753G>A) pathogenic?

PRRT2 p.Leu251= (c.753G>A) is classified Likely benign in PRRT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-24). Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with PRRT2 p.Leu251= (c.753G>A)?

PRRT2 p.Leu251= (c.753G>A) is associated with Inborn genetic diseases, episodic kinesigenic dyskinesia (ClinVar).

How common is PRRT2 p.Leu251= (c.753G>A) in the general population?

PRRT2 p.Leu251= (c.753G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

PRRT2 p.Leu251=

c.753G>A · rs770596922 · VCV1142044

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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
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 2	GERP -1.4, phastCons 1
Overall
CADD	6.549	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,840 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,612,622 alleles · very rare exomes 2/1,460,514 · genomes 1/152,108 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,420
European (non-Finnish)	8.48e-05%	1,179,363

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.Leu251=
Coding: c.753G>A
MANE Select: NM_145239
dbSNP: rs770596922
Type: single nucleotide variant
Location: chr16:29813807 (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-leu251 (accessed [today's date]).

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