Is LDB3 p.Pro502= (c.1506G>A) pathogenic?

LDB3 p.Pro502= (c.1506G>A) is classified Benign in LDB3 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-01). Low-frequency (popmax 3.06%, afr); Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Pro502= (c.1506G>A)?

LDB3 p.Pro502= (c.1506G>A) is associated with Cardiovascular phenotype, cardiomyopathy, myofibrillar myopathy 4 (ClinVar).

How common is LDB3 p.Pro502= (c.1506G>A) in the general population?

LDB3 p.Pro502= (c.1506G>A) is low-frequency (popmax 3.06%, afr) (gnomAD).

LDB3 p.Pro502=

c.1506G>A · rs45579241 · VCV45526

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.06%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.87	GERP -3.8, phastCons 0.013
Overall
CADD	8.577	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.06% African / African-American · 2,290/74,860 alleles

Filtering AF 2.95% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.91%

Overall 0.157% 2,537/1,613,764 alleles · low-frequency exomes 1,240/1,461,838 · genomes 1,297/151,926 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.06%	33
Remaining individualsnot grpmax-eligible	0.173%	579
Admixed American	0.135%	741
Middle Eastern	0.0495%	2,021
South Asian	0.0231%	4,336
Finnishnot grpmax-eligible	0.00469%	21,321
European (non-Finnish)	0.00263%	38,063

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.Pro502=
Coding: c.1506G>A
MANE Select: NM_007078
dbSNP: rs45579241
Type: single nucleotide variant
Location: chr10:86716601 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 502: 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 myofibrillar myopathy 4

Similar variants

LDB3 p.Pro502Leu 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-pro502 (accessed [today's date]).

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