Is PLN p.Arg9= (c.27C>A) pathogenic?

PLN p.Arg9= (c.27C>A) is classified Likely benign in PLN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-10). Absent from gnomAD v4.1; Associated with dilated cardiomyopathy 1P.

What condition is associated with PLN p.Arg9= (c.27C>A)?

PLN p.Arg9= (c.27C>A) is associated with dilated cardiomyopathy 1P (ClinVar).

How common is PLN p.Arg9= (c.27C>A) in the general population?

PLN p.Arg9= (c.27C>A) 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.

PLN p.Arg9=

c.27C>A · rs145623013 · VCV511655

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

dilated cardiomyopathy 1P

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 1.3, phastCons 1
Overall
CADD	9.715	PHRED · no single calibrated threshold — expert panels disagree

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.Arg9=
Coding: c.27C>A
MANE Select: NM_002667
dbSNP: rs145623013
Type: single nucleotide variant
Location: chr6:118558948 (GRCh38)
Gene constraint: LOEUF 1.704 · pLI 0.42 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 81.81 · 7 PDB
Residue 9: a UniProt-annotated variant site (in cmd1p; impairs phosphorylation by pka and inhibition of atp2a1-mediated calcium uptake)

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.Arg9Leu Likely pathogenic ★ ⚠ 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-arg9 (accessed [today's date]).

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