Is LDB3 p.Cys697= (c.2091C>T) pathogenic?

LDB3 p.Cys697= (c.2091C>T) is classified Benign/Likely benign in LDB3 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-10-22). Rare (popmax 0.166%, mid); Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Cys697= (c.2091C>T)?

LDB3 p.Cys697= (c.2091C>T) is associated with Cardiovascular phenotype, myofibrillar myopathy 4 (ClinVar).

How common is LDB3 p.Cys697= (c.2091C>T) in the general population?

LDB3 p.Cys697= (c.2091C>T) is rare (popmax 0.166%, mid) (gnomAD).

LDB3 p.Cys697=

c.2091C>T · rs571356142 · VCV179942

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.166%, mid)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.20	donor loss · deltas
Constraint at this position
Conservation	phyloP -3.4	GERP -4.6
Overall
CADD	5.507	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.166% Middle Eastern · 10/6,014 alleles

Filtering AF 0.0944% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0878%

Overall 0.00986% 159/1,612,932 alleles · rare exomes 151/1,460,662 · genomes 8/152,270 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.166%	601
South Asian	0.112%	893
Remaining individualsnot grpmax-eligible	0.0064%	15,617
East Asian	0.00446%	22,436
European (non-Finnish)	0.00348%	28,756

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.Cys697=
Coding: c.2091C>T
MANE Select: NM_007078
dbSNP: rs571356142
Type: single nucleotide variant
Location: chr10:86726249 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 697: a UniProt-annotated variant site (in cmd2l; likely pathogenic); the lim zinc-binding 3 domain

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-cys697 (accessed [today's date]).

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