Is LDB3 p.Asp289= (c.867C>T) pathogenic?

LDB3 p.Asp289= (c.867C>T) is classified Benign/Likely benign in LDB3 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-25). Ultra-rare (popmax 0.0624%, eas); Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Asp289= (c.867C>T)?

LDB3 p.Asp289= (c.867C>T) is associated with Cardiovascular phenotype, myofibrillar myopathy 4 (ClinVar).

How common is LDB3 p.Asp289= (c.867C>T) in the general population?

LDB3 p.Asp289= (c.867C>T) is ultra-rare (popmax 0.0624%, eas) (gnomAD).

LDB3 p.Asp289=

c.867C>T · rs397517227 · VCV45557

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0624%, eas)

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 1.8	GERP 1.3, phastCons 1
Overall
CADD	11.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0624% East Asian · 28/44,888 alleles

Filtering AF 0.0443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0382%

Overall 0.00192% 31/1,614,182 alleles · ultra-rare exomes 25/1,461,844 · genomes 6/152,338 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0624%	1,603
Remaining individualsnot grpmax-eligible	0.0032%	31,254
European (non-Finnish)	8.47e-05%	1,179,998

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.Asp289=
Coding: c.867C>T
MANE Select: NM_007078
dbSNP: rs397517227
Type: single nucleotide variant
Location: chr10:86692542 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 289: 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: 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-asp289 (accessed [today's date]).

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