Is LDB3 p.Asp168= (c.504T>C) pathogenic?

LDB3 p.Asp168= (c.504T>C) is classified Benign/Likely benign in LDB3 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-04). Common (popmax 14.7%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Asp168= (c.504T>C)?

LDB3 p.Asp168= (c.504T>C) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1C, myofibrillar myopathy 4 (ClinVar).

LDB3 p.Asp168=

Q: How common is LDB3 p.Asp168= (c.504T>C) in the general population?

LDB3 p.Asp168= (c.504T>C) is common (popmax 14.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.504T>C · rs76615432 · VCV43879

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Common

common (popmax 14.7%, afr) — too common for a highly-penetrant pathogenic allele

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 -7.4	GERP -4.2
Overall
CADD	7.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.7% African / African-American · 11,000/75,024 alleles

Filtering AF 14.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.3%

Overall 4.1% 66,170/1,614,128 alleles · common exomes 56,175/1,461,862 · genomes 9,995/152,266 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	14.7%	7
Middle Eastern	8.69%	12
Ashkenazi Jewishnot grpmax-eligible	5.22%	19
Remaining individualsnot grpmax-eligible	4.72%	21
European (non-Finnish)	3.64%	27
South Asian	3.52%	28
Finnishnot grpmax-eligible	3.45%	29
Admixed American	2.88%	35
Amishnot grpmax-eligible	2.85%	35
East Asian	0.154%	650

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.Asp168=
Coding: c.504T>C
MANE Select: NM_007078 · reported on NM_001368067
dbSNP: rs76615432
Type: single nucleotide variant
Location: chr10:86687228 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 168: 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: dilated cardiomyopathy 1C myofibrillar myopathy 4

Similar variants

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
LDB3 c.859+5G>C 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-asp168 (accessed [today's date]).

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