Is LDB3 p.Ala501Val (c.1502C>T) pathogenic?

LDB3 p.Ala501Val (c.1502C>T) is classified Uncertain significance in LDB3 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-07-22). AlphaMissense: likely benign (0.0911); Very rare (popmax 0.00223%, eas); Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Ala501Val (c.1502C>T)?

LDB3 p.Ala501Val (c.1502C>T) is associated with Cardiovascular phenotype, cardiomyopathy, dilated cardiomyopathy 1C (ClinVar).

How common is LDB3 p.Ala501Val (c.1502C>T) in the general population?

LDB3 p.Ala501Val (c.1502C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about LDB3 p.Ala501Val (c.1502C>T)?

AlphaMissense predicts likely benign (score 0.0911) — an in-silico prediction, not a clinical call.

LDB3 p.Ala501Val

c.1502C>T · rs755362259 · VCV426972

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0911 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0911	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -8.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 64 kb · p 0.14 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,864 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00105% 17/1,613,708 alleles · very rare exomes 16/1,461,838 · genomes 1/151,870 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,864
European (non-Finnish)	0.00136%	73,748

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.Ala501Val
Coding: c.1502C>T
MANE Select: NM_007078
dbSNP: rs755362259
Type: single nucleotide variant
Location: chr10:86716597 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 501: 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

Also linked: cardiomyopathy dilated cardiomyopathy 1C myofibrillar myopathy 4

Similar variants

LDB3 p.Ala501= Likely benign ★★ same residue
LDB3 p.Ala501Thr 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

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-ala501val (accessed [today's date]).

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