Is PLN p.Phe35fs (c.105_106del) pathogenic?

PLN p.Phe35fs (c.105106del) is classified Pathogenic in PLN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-30). Very rare (popmax 0.0011%, sas); Associated with dilated cardiomyopathy 1P.

What condition is associated with PLN p.Phe35fs (c.105_106del)?

PLN p.Phe35fs (c.105_106del) is associated with dilated cardiomyopathy 1P (ClinVar).

How common is PLN p.Phe35fs (c.105_106del) in the general population?

PLN p.Phe35fs (c.105_106del) is very rare (popmax 0.0011%, sas) (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.Phe35fs

c.105_106del · rs747947483 · VCV1977709

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

dilated cardiomyopathy 1P

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,010 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000206% 3/1,458,226 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,010
European (non-Finnish)	0.00017%	588,370

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.Phe35fs
Coding: c.105_106del
MANE Select: NM_002667
dbSNP: rs747947483
Type: Deletion
Location: chr6:118559025 (GRCh38)
Gene constraint: LOEUF 1.704 · pLI 0.42 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 81.81 · 7 PDB
Residue 35: an α-helix

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 c.-97-?_*1344+?del Pathogenic ★ same condition
PLN p.Phe32fs Pathogenic ★ same condition
PLN p.Val49fs Uncertain significance ★ same condition
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

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-phe35fs (accessed [today's date]).

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