Is LDB3 p.Val239Ala (c.716T>C) pathogenic?

LDB3 p.Val239Ala (c.716T>C) is classified Uncertain significance in LDB3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-02-06). AlphaMissense: ambiguous (0.5114); Very rare (popmax 0.000763%, nfe); Associated with dilated cardiomyopathy 1C.

What condition is associated with LDB3 p.Val239Ala (c.716T>C)?

LDB3 p.Val239Ala (c.716T>C) is associated with dilated cardiomyopathy 1C, myofibrillar myopathy 4 (ClinVar).

How common is LDB3 p.Val239Ala (c.716T>C) in the general population?

LDB3 p.Val239Ala (c.716T>C) is very rare (popmax 0.000763%, nfe) (gnomAD).

How is Left ventricular noncompaction inherited?

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

What do computational predictors say about LDB3 p.Val239Ala (c.716T>C)?

AlphaMissense predicts ambiguous (score 0.5114) — an in-silico prediction, not a clinical call.

LDB3 p.Val239Ala

c.716T>C · rs774595610 · VCV1415919

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.5114 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Conditions

dilated cardiomyopathy 1C

Computational evidence

Protein change
AlphaMissense	0.5114	ambiguous
REVEL	0.514	indeterminate
SaProt	LLR -7.80	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 64 kb · p 0.14 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,180,038 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000558% 9/1,614,038 alleles · very rare exomes 8/1,461,844 · genomes 1/152,194 · 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.Val239Ala
Coding: c.716T>C
MANE Select: NM_007078
dbSNP: rs774595610
Type: single nucleotide variant
Location: chr10:86691922 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB

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 p.Val239Ile Conflicting classifications of pathogenicity ★ ⚠ 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-val239ala (accessed [today's date]).

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