Is LDB3 p.Ile725= (c.2175C>T) pathogenic?

LDB3 p.Ile725= (c.2175C>T) is classified Conflicting classifications of pathogenicity in LDB3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-11-29). Very rare (popmax 0.00167%, amr); Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Ile725= (c.2175C>T)?

LDB3 p.Ile725= (c.2175C>T) is associated with Cardiovascular phenotype, myofibrillar myopathy 4 (ClinVar).

How common is LDB3 p.Ile725= (c.2175C>T) in the general population?

LDB3 p.Ile725= (c.2175C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

LDB3 p.Ile725=

c.2175C>T · rs1413752114 · VCV1977007

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 2.6	GERP -1.1, phastCons 1
Overall
CADD	6.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,952 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,613,268 alleles · very rare exomes 3/1,460,992 · genomes 1/152,276 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,952
European (non-Finnish)	0.000254%	393,201

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.Ile725=
Coding: c.2175C>T
MANE Select: NM_007078
dbSNP: rs1413752114
Type: single nucleotide variant
Location: chr10:86732967 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 725: 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.Ile725Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
LDB3 p.Ile725Leu Uncertain significance ★ ⚠ same residue
LDB3 p.Ile725Thr Uncertain significance ★ ⚠ same residue
LDB3 p.Ile725Val 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

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-ile725 (accessed [today's date]).

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