Is PKP2 p.Val271Phe (c.811G>T) pathogenic?

PKP2 p.Val271Phe (c.811G>T) is classified Uncertain significance in PKP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-04). AlphaMissense: likely benign (0.1167); Absent from gnomAD v4.1; Associated with cardiomyopathy.

What condition is associated with PKP2 p.Val271Phe (c.811G>T)?

PKP2 p.Val271Phe (c.811G>T) is associated with cardiomyopathy (ClinVar).

How common is PKP2 p.Val271Phe (c.811G>T) in the general population?

PKP2 p.Val271Phe (c.811G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PKP2 p.Val271Phe (c.811G>T)?

AlphaMissense predicts likely benign (score 0.1167) — an in-silico prediction, not a clinical call.

PKP2 p.Val271Phe

c.811G>T · rs876657953 · VCV921150

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1167 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.1167	likely benign
REVEL	0.255	benign-leaning
SaProt	LLR -8.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.41	phastCons 0.01
Regional constraint	o/e 0.91	unconstrained · MANE · 104 kb · p 0.0023 · regional, not allelic
Overall
CADD	11.14	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: PKP2
Protein: p.Val271Phe
Coding: c.811G>T
MANE Select: NM_001005242
dbSNP: rs876657953
Type: single nucleotide variant
Location: chr12:32878069 (GRCh38)
Gene constraint: LOEUF 1.105 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.32 · 1 PDB
Residue 271: the 'required for interaction with influenza a virus rna polymerase subunit pb1' region; a UniProt-annotated variant site (in arvd9; uncertain significance); the 'required for binding to single-stranded dna' region

Full PKP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PKP2 p.Val271Ile Uncertain significance ★★ ⚠ same residue
PKP2 p.Val271= Uncertain significance ★ same residue
PKP2 p.Val271Gly Uncertain significance ★ ⚠ same residue
PKP2 c.1034+1G>C Likely pathogenic ★★ same condition
PKP2 c.1034+1G>T Likely pathogenic ★★ same condition
PKP2 c.1170+1G>A Pathogenic/Likely pathogenic ★★ same condition
PKP2 c.1171-2A>G Pathogenic/Likely pathogenic ★★ same condition
PKP2 c.1378+1G>A Pathogenic/Likely pathogenic ★★ same condition

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/pkp2-p-val271phe (accessed [today's date]).

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