Is LDB3 p.Pro357= (c.1071T>A) pathogenic?

LDB3 p.Pro357= (c.1071T>A) is classified Conflicting classifications of pathogenicity in LDB3 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-11-27). Ultra-rare (popmax 0.018%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Pro357= (c.1071T>A)?

LDB3 p.Pro357= (c.1071T>A) is associated with Cardiovascular phenotype, cardiomyopathy, myofibrillar myopathy 4 (ClinVar).

How common is LDB3 p.Pro357= (c.1071T>A) in the general population?

LDB3 p.Pro357= (c.1071T>A) is ultra-rare (popmax 0.018%, nfe) (gnomAD).

LDB3 p.Pro357=

c.1071T>A · rs143823978 · VCV178060

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.018%, nfe)

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 -0.065	GERP -1.5, phastCons 0.38
Overall
CADD	0.787	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.018% European (non-Finnish) · 212/1,179,540 alleles

Filtering AF 0.016% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0152%

Overall 0.0139% 224/1,612,118 alleles · ultra-rare exomes 212/1,459,938 · genomes 12/152,180 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.018%	5,564
Remaining individualsnot grpmax-eligible	0.0112%	8,911
African / African-American	0.00534%	18,724
East Asian	0.00223%	44,874

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.Pro357=
Coding: c.1071T>A
MANE Select: NM_007078
dbSNP: rs143823978
Type: single nucleotide variant
Location: chr10:86706705 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 357: 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: cardiomyopathy myofibrillar myopathy 4

Similar variants

LDB3 p.Pro357Ser 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
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

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-pro357 (accessed [today's date]).

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