Is LDB3 p.Lys499fs (c.1495_1529del) pathogenic?

LDB3 p.Lys499fs (c.14951529del) is classified Uncertain significance in LDB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-06). Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Lys499fs (c.1495_1529del)?

LDB3 p.Lys499fs (c.1495_1529del) is associated with Cardiovascular phenotype (ClinVar).

LDB3 p.Lys499fs

c.1495_1529del · VCV3537679

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Cardiovascular phenotype

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 10 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.21	GERP -3.8, phastCons 0.99

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

Variant & gene context

Gene: LDB3
Protein: p.Lys499fs
Coding: c.1495_1529del
MANE Select: NM_007078
Type: Deletion
Location: chr10:86716587 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 499: the 'disordered' region

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LDB3 p.Lys499Asn Uncertain significance ★★ ⚠ same residue
LDB3 p.Lys499= Likely benign ★ same residue
LDB3 p.Glu483_Ala485del Uncertain significance ★★ same condition
LDB3 p.Val676fs Uncertain significance ★★ same condition
LDB3 c.116_245+122del Uncertain significance ★ same condition
LDB3 c.897-2195_1046del Uncertain significance ★ same condition
LDB3 p.Gln537fs Conflicting classifications of pathogenicity ★ same condition
LDB3 p.Glu592fs Conflicting classifications of pathogenicity ★ 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-lys499fs (accessed [today's date]).

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