Is LDB3 p.Arg296Ter (c.886C>T) pathogenic?

LDB3 p.Arg296Ter (c.886C>T) is classified Conflicting classifications of pathogenicity in LDB3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-22). Very rare (popmax 0.00133%, afr); Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Arg296Ter (c.886C>T)?

LDB3 p.Arg296Ter (c.886C>T) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1C, myofibrillar myopathy 4 (ClinVar).

How common is LDB3 p.Arg296Ter (c.886C>T) in the general population?

LDB3 p.Arg296Ter (c.886C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

LDB3 p.Arg296Ter

c.886C>T · rs1060501316 · VCV406804

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 14
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP 2.4, phastCons 0.99
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,934 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.00062% 10/1,614,066 alleles · very rare exomes 9/1,461,840 · genomes 1/152,226 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,934
South Asian	0.0011%	91,088
European (non-Finnish)	0.000678%	147,501

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.Arg296Ter
Coding: c.886C>T
MANE Select: NM_007078
dbSNP: rs1060501316
Type: single nucleotide variant
Location: chr10:86692561 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 296: 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.Arg296Gln Uncertain significance ★★ ⚠ same residue
LDB3 p.Arg296= Likely benign ★★ 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-arg296ter (accessed [today's date]).

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