Is LDB3 p.Pro642= (c.1926T>G) pathogenic?

LDB3 p.Pro642= (c.1926T>G) is classified Likely benign in LDB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-12). Very rare (popmax 8.47e-05%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Pro642= (c.1926T>G)?

LDB3 p.Pro642= (c.1926T>G) is associated with Cardiovascular phenotype (ClinVar).

How common is LDB3 p.Pro642= (c.1926T>G) in the general population?

LDB3 p.Pro642= (c.1926T>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

LDB3 p.Pro642=

c.1926T>G · VCV4046678

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, 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 0.18	GERP -0.22, phastCons 0.98
Overall
CADD	8.545	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,002 alleles

Overall 6.2e-05% 1/1,614,102 alleles · very rare exomes 1/1,461,872 · genomes 0/152,230 · joint denominator

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.Pro642=
Coding: c.1926T>G
MANE Select: NM_007078
Type: single nucleotide variant
Location: chr10:86718795 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 642: the lim zinc-binding 2 domain; a UniProt-annotated variant site (in cmd2l; likely pathogenic)

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

Similar variants

LDB3 p.Pro642Ala Uncertain significance ★ ⚠ same residue
LDB3 p.Pro642His Uncertain significance ★ ⚠ same residue
LDB3 c.246-3C>T Uncertain significance ★★ same condition
LDB3 c.860-3C>T Uncertain significance ★★ same condition
LDB3 p.Ala119Val Uncertain significance ★★ ⚠ same condition
LDB3 p.Ala126Val Uncertain significance ★★ ⚠ same condition
LDB3 p.Ala248Thr Uncertain significance ★★ same condition
LDB3 p.Ala264Thr 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-pro642 (accessed [today's date]).

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