Is LDB3 p.Pro608= (c.1824G>T) pathogenic?

LDB3 p.Pro608= (c.1824G>T) is classified Conflicting classifications of pathogenicity in LDB3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-03). Very rare (popmax 8.47e-05%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Pro608= (c.1824G>T)?

LDB3 p.Pro608= (c.1824G>T) is associated with Cardiovascular phenotype, myofibrillar myopathy 4 (ClinVar).

How common is LDB3 p.Pro608= (c.1824G>T) in the general population?

LDB3 p.Pro608= (c.1824G>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

LDB3 p.Pro608=

c.1824G>T · rs748428531 · VCV1780819

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.29	donor gain · deltas
Constraint at this position
Conservation	phyloP -6.1	GERP -4.6
Overall
CADD	1.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,034 alleles

Overall 6.2e-05% 1/1,614,160 alleles · very rare exomes 1/1,461,874 · genomes 0/152,286 · joint denominator

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.Pro608=
Coding: c.1824G>T
MANE Select: NM_007078
dbSNP: rs748428531
Type: single nucleotide variant
Location: chr10:86718111 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 608: the lim zinc-binding 2 domain; a UniProt-annotated variant site (in cmd2l; likely pathogenic); a UniProt-annotated variant site (in cmh24; uncertain significance)

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

Also linked: myofibrillar myopathy 4

Similar variants

LDB3 p.Pro608Leu Uncertain significance ★★ ⚠ same residue
LDB3 p.Ala147Thr Pathogenic/Likely pathogenic ★★ same condition
LDB3 p.Ala165Val Pathogenic/Likely pathogenic ★★ same condition
LDB3 c.1231+4A>C Uncertain significance ★★ same condition
LDB3 c.1858-11C>A Uncertain significance ★★ same condition
LDB3 c.246-3C>T Uncertain significance ★★ same condition
LDB3 c.322-1G>A Uncertain significance ★★ same condition
LDB3 c.859+3G>A 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/ldb3-p-pro608 (accessed [today's date]).

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