Is PRRT2 p.Leu271Val (c.811C>G) pathogenic?

PRRT2 p.Leu271Val (c.811C>G) is classified Uncertain significance in PRRT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-08-01). AlphaMissense: ambiguous (0.461); Absent from gnomAD v4.1.

How common is PRRT2 p.Leu271Val (c.811C>G) in the general population?

PRRT2 p.Leu271Val (c.811C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRRT2 p.Leu271Val (c.811C>G)?

AlphaMissense predicts ambiguous (score 0.461) — an in-silico prediction, not a clinical call.

PRRT2 p.Leu271Val

c.811C>G · rs1596892978 · VCV808027

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.461 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

⚠ 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	0.461	ambiguous
REVEL	0.664	pathogenic-leaning
SaProt	LLR -11.05	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 84 bp · p 0.0007 · regional, not allelic
Overall
CADD	25.6	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.Leu271Val
Coding: c.811C>G
MANE Select: NM_145239
dbSNP: rs1596892978
Type: single nucleotide variant
Location: chr16:29813865 (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-leu271val (accessed [today's date]).

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