Is LDB3 p.Val239Ile (c.715G>A) pathogenic?

LDB3 p.Val239Ile (c.715G>A) is classified Conflicting classifications of pathogenicity in LDB3 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-08-04). AlphaMissense: likely benign (0.093); Rare (popmax 0.115%, mid); Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Val239Ile (c.715G>A)?

LDB3 p.Val239Ile (c.715G>A) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1C, myofibrillar myopathy 4 (ClinVar).

How common is LDB3 p.Val239Ile (c.715G>A) in the general population?

LDB3 p.Val239Ile (c.715G>A) is rare (popmax 0.115%, mid) (gnomAD).

What do computational predictors say about LDB3 p.Val239Ile (c.715G>A)?

AlphaMissense predicts likely benign (score 0.093) — an in-silico prediction, not a clinical call.

LDB3 p.Val239Ile

c.715G>A · rs201417512 · VCV191697

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.093 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.115%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.093	likely benign
REVEL	0.373	indeterminate
SaProt	LLR -6.12	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 64 kb · p 0.14 · regional, not allelic
Overall
CADD	22.0	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 0.115% Middle Eastern · 7/6,062 alleles

Filtering AF 0.0542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0384%

Overall 0.00917% 148/1,614,132 alleles · rare exomes 134/1,461,842 · genomes 14/152,290 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.115%	866
Finnishnot grpmax-eligible	0.0328%	3,047
East Asian	0.0245%	4,079
European (non-Finnish)	0.00814%	12,292
Remaining individualsnot grpmax-eligible	0.008%	12,502
African / African-American	0.00533%	18,764
South Asian	0.00329%	30,355
Admixed American	0.00167%	60,024

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.Val239Ile
Coding: c.715G>A
MANE Select: NM_007078
dbSNP: rs201417512
Type: single nucleotide variant
Location: chr10:86691921 (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

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

Also linked: dilated cardiomyopathy 1C myofibrillar myopathy 4

Similar variants

LDB3 p.Val239Ala 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-val239ile (accessed [today's date]).

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