Is LDB3 p.Ser182= (c.546T>C) pathogenic?

LDB3 p.Ser182= (c.546T>C) is classified Benign in LDB3 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-03). Low-frequency (popmax 1.5%, mid); Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Ser182= (c.546T>C)?

LDB3 p.Ser182= (c.546T>C) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1C, myofibrillar myopathy 4 (ClinVar).

How common is LDB3 p.Ser182= (c.546T>C) in the general population?

LDB3 p.Ser182= (c.546T>C) is low-frequency (popmax 1.5%, mid) (gnomAD).

LDB3 p.Ser182=

c.546T>C · rs71473272 · VCV43880

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.5%, mid)

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 -0.67	GERP -3.5, phastCons 0.035
Overall
CADD	11.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.5% Middle Eastern · 91/6,058 alleles

Filtering AF 1.25% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.16%

Overall 0.444% 7,163/1,613,964 alleles · low-frequency exomes 6,627/1,461,762 · genomes 536/152,202 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.5%	67
Ashkenazi Jewishnot grpmax-eligible	1.38%	73
South Asian	1.21%	83
Remaining individualsnot grpmax-eligible	0.536%	187
Admixed American	0.423%	236
European (non-Finnish)	0.417%	240
African / African-American	0.0613%	1,630
Finnishnot grpmax-eligible	0.0125%	7,997
East Asian	0.00669%	14,957

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.Ser182=
Coding: c.546T>C
MANE Select: NM_007078 · reported on NM_001368067
dbSNP: rs71473272
Type: single nucleotide variant
Location: chr10:86687270 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 182: 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: dilated cardiomyopathy 1C myofibrillar myopathy 4

Similar variants

LDB3 p.Gly182Asp Uncertain significance ★★ ⚠ same residue
LDB3 p.Gly182Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
LDB3 p.Ser182Arg Uncertain significance ★ same residue
LDB3 p.Ser182Cys Uncertain significance ★ same residue
LDB3 p.Gly182= Likely benign ★ 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

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-ser182 (accessed [today's date]).

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