Is PLN p.Ala11Pro (c.31G>C) pathogenic?

PLN p.Ala11Pro (c.31G>C) is classified Uncertain significance in PLN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-28). AlphaMissense: likely pathogenic (0.8853); Absent from gnomAD v4.1; Associated with dilated cardiomyopathy 1P.

What condition is associated with PLN p.Ala11Pro (c.31G>C)?

PLN p.Ala11Pro (c.31G>C) is associated with dilated cardiomyopathy 1P (ClinVar).

How common is PLN p.Ala11Pro (c.31G>C) in the general population?

PLN p.Ala11Pro (c.31G>C) 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.Ala11Pro (c.31G>C)?

AlphaMissense predicts likely pathogenic (score 0.8853) — an in-silico prediction, not a clinical call.

PLN p.Ala11Pro

c.31G>C · rs2114969616 · VCV2090664

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8853 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dilated cardiomyopathy 1P

⚠ 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	0.8853	likely pathogenic
REVEL	0.932	strongly pathogenic-leaning
SaProt	LLR -14.09	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 155 bp · p 0.64 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Ala11Pro
Coding: c.31G>C
MANE Select: NM_002667
dbSNP: rs2114969616
Type: single nucleotide variant
Location: chr6:118558952 (GRCh38)

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)

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-ala11pro (accessed [today's date]).

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