Is LDB3 p.Glu386= (c.1158G>A) pathogenic?

LDB3 p.Glu386= (c.1158G>A) is classified Likely benign in LDB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-02-09). Very rare (popmax 0.00167%, amr); Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Glu386= (c.1158G>A)?

LDB3 p.Glu386= (c.1158G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is LDB3 p.Glu386= (c.1158G>A) in the general population?

LDB3 p.Glu386= (c.1158G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

LDB3 p.Glu386=

c.1158G>A · rs45465300 · VCV518612

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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 2.1	GERP -1, phastCons 1
Overall
CADD	3.215	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,012 alleles

Overall 6.2e-05% 1/1,613,098 alleles · very rare exomes 1/1,460,790 · genomes 0/152,308 · 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.Glu386=
Coding: c.1158G>A
MANE Select: NM_007078
dbSNP: rs45465300
Type: single nucleotide variant
Location: chr10:86709977 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 386: 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

Similar variants

LDB3 p.Glu386Lys 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
LDB3 p.Ala365Asp 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-glu386 (accessed [today's date]).

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