Is PLN p.Ile48= (c.144C>T) pathogenic?

PLN p.Ile48= (c.144C>T) is classified Likely benign in PLN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-26). Very rare (popmax 0.00935%, afr); Associated with dilated cardiomyopathy 1P.

What condition is associated with PLN p.Ile48= (c.144C>T)?

PLN p.Ile48= (c.144C>T) is associated with dilated cardiomyopathy 1P (ClinVar).

How common is PLN p.Ile48= (c.144C>T) in the general population?

PLN p.Ile48= (c.144C>T) is very rare (popmax 0.00935%, afr) (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.Ile48=

c.144C>T · rs141114252 · VCV700703

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -3.3	GERP -4.3
Overall
CADD	4.282	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00935% African / African-American · 7/74,860 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000745% 12/1,610,948 alleles · very rare exomes 5/1,458,746 · genomes 7/152,202 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,694
South Asian	0.0022%	45,518
European (non-Finnish)	0.000255%	392,405

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PLN
Protein: p.Ile48=
Coding: c.144C>T
MANE Select: NM_002667
dbSNP: rs141114252
Type: single nucleotide variant
Location: chr6:118559065 (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-ile48 (accessed [today's date]).

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