Is PLN p.Leu7Phe (c.19C>T) pathogenic?

PLN p.Leu7Phe (c.19C>T) is classified Uncertain significance in PLN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-29). AlphaMissense: likely benign (0.0833); Absent from gnomAD v4.1; Associated with dilated cardiomyopathy 1P.

What condition is associated with PLN p.Leu7Phe (c.19C>T)?

PLN p.Leu7Phe (c.19C>T) is associated with dilated cardiomyopathy 1P (ClinVar).

How common is PLN p.Leu7Phe (c.19C>T) in the general population?

PLN p.Leu7Phe (c.19C>T) is absent from gnomAD v4.1 (gnomAD).

How is Familial isolated dilated cardiomyopathy inherited?

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

What do computational predictors say about PLN p.Leu7Phe (c.19C>T)?

AlphaMissense predicts likely benign (score 0.0833) — an in-silico prediction, not a clinical call.

PLN p.Leu7Phe

c.19C>T · VCV4738817

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0833 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

dilated cardiomyopathy 1P

Computational evidence

Protein change
AlphaMissense	0.0833	likely benign
REVEL	0.514	indeterminate
SaProt	LLR -7.42	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 155 bp · p 0.64 · regional, not allelic
Overall
CADD	25.3	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: PLN
Protein: p.Leu7Phe
Coding: c.19C>T
MANE Select: NM_002667
Type: single nucleotide variant
Location: chr6:118558940 (GRCh38)
Gene constraint: LOEUF 1.704 · pLI 0.42 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 81.81 · 7 PDB

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

Disease context

dilated cardiomyopathy 1P — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial isolated dilated cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

PLN p.Leu7= Likely benign ★ same residue
PLN c.-120C>T Uncertain significance ★★ same condition
PLN c.-97-5T>C Uncertain significance ★★ same condition
PLN c.*1225C>T Uncertain significance ★★ same condition
PLN c.*1243C>T Uncertain significance ★★ same condition
PLN c.*277A>G Uncertain significance ★★ same condition
PLN p.Arg25Gly Uncertain significance ★★ ⚠ same condition
PLN p.Ile12Met Uncertain significance ★★ ⚠ 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/pln-p-leu7phe (accessed [today's date]).

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