Is PRRT2 p.Pro279Ala (c.835C>G) pathogenic?

PRRT2 p.Pro279Ala (c.835C>G) is classified Likely pathogenic in PRRT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-12-20). AlphaMissense: likely pathogenic (0.9813); Absent from gnomAD v4.1; Associated with seizures, benign familial infantile, 2.

What condition is associated with PRRT2 p.Pro279Ala (c.835C>G)?

PRRT2 p.Pro279Ala (c.835C>G) is associated with seizures, benign familial infantile, 2 (ClinVar).

How common is PRRT2 p.Pro279Ala (c.835C>G) in the general population?

PRRT2 p.Pro279Ala (c.835C>G) is absent from gnomAD v4.1 (gnomAD).

How is Self-limited infantile epilepsy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about PRRT2 p.Pro279Ala (c.835C>G)?

AlphaMissense predicts likely pathogenic (score 0.9813) — an in-silico prediction, not a clinical call.

PRRT2 p.Pro279Ala

c.835C>G · rs2543336371 · VCV813802

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9813 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

seizures, benign familial infantile, 2

⚠ 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	0.9813	likely pathogenic ✓ concordant with ClinVar
REVEL	0.774	moderately pathogenic-leaning
SaProt	LLR -11.85	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 84 bp · p 0.0007 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRRT2
Protein: p.Pro279Ala
Coding: c.835C>G
MANE Select: NM_145239
dbSNP: rs2543336371
Type: single nucleotide variant
Location: chr16:29813889 (GRCh38)

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

Disease context

seizures, benign familial infantile, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Self-limited infantile epilepsy (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

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-pro279ala (accessed [today's date]).

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