Is LDB3 p.Pro183fs (c.548del) pathogenic?

LDB3 p.Pro183fs (c.548del) is classified Conflicting classifications of pathogenicity in LDB3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-18). Very rare (popmax 0.000254%, nfe); Associated with dilated cardiomyopathy 1C.

What condition is associated with LDB3 p.Pro183fs (c.548del)?

LDB3 p.Pro183fs (c.548del) is associated with dilated cardiomyopathy 1C, myofibrillar myopathy 4 (ClinVar).

How common is LDB3 p.Pro183fs (c.548del) in the general population?

LDB3 p.Pro183fs (c.548del) is very rare (popmax 0.000254%, nfe) (gnomAD).

How is Left ventricular noncompaction inherited?

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

LDB3 p.Pro183fs

c.548del · rs1285270306 · VCV518778

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

dilated cardiomyopathy 1C

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP 0.79, phastCons 1
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,874 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,613,144 alleles · very rare exomes 3/1,460,896 · genomes 1/152,248 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,462
European (non-Finnish)grpmax	0.000254%	393,292

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: LDB3
Protein: p.Pro183fs
Coding: c.548del
MANE Select: NM_007078
dbSNP: rs1285270306
Type: Deletion
Location: chr10:86681660 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 183: the 'disordered' region

Full LDB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: myofibrillar myopathy 4

For Left ventricular noncompaction (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages

Similar variants

LDB3 c.860-22_860-12del Uncertain significance ★★ same condition
LDB3 p.Glu483_Ala485del Uncertain significance ★★ same condition
LDB3 p.Val676fs Uncertain significance ★★ same condition
LDB3 c.1086-247_1231+2del Pathogenic ★ same condition
LDB3 p.Ala319fs Likely pathogenic ★ same condition
LDB3 p.Arg559fs Pathogenic ★ same condition
LDB3 p.Gln81fs Pathogenic ★ same condition
LDB3 p.Gly131fs Pathogenic ★ 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/ldb3-p-pro183fs (accessed [today's date]).

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