Is LDB3 p.Ser347= (c.1041C>A) pathogenic?

LDB3 p.Ser347= (c.1041C>A) is classified Benign in LDB3 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-03). Common (popmax 16.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Ser347= (c.1041C>A)?

LDB3 p.Ser347= (c.1041C>A) is associated with Cardiovascular phenotype, cardiomyopathy, dilated cardiomyopathy 1C (ClinVar).

LDB3 p.Ser347=

Q: How common is LDB3 p.Ser347= (c.1041C>A) in the general population?

LDB3 p.Ser347= (c.1041C>A) is common (popmax 16.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1041C>A · rs45555240 · VCV36442

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 16.2%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.2	GERP -3.9, phastCons 0.73
Overall
CADD	0.232	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 16.2% African / African-American · 12,167/75,024 alleles

Filtering AF 16% ClinGen BA1/BS1 input FAF95, joint · FAF99 15.9%

Overall 0.937% 15,119/1,612,904 alleles · common exomes 8,068/1,460,592 · genomes 7,051/152,312 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	16.2%	6
Remaining individualsnot grpmax-eligible	1.43%	70
Middle Eastern	1.35%	74
Admixed American	1.26%	79
Ashkenazi Jewishnot grpmax-eligible	0.487%	205
East Asian	0.484%	207
South Asian	0.412%	243
European (non-Finnish)	0.0413%	2,423

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.Ser347=
Coding: c.1041C>A
MANE Select: NM_007078
dbSNP: rs45555240
Type: single nucleotide variant
Location: chr10:86706675 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 347: 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 dilated cardiomyopathy 1C myofibrillar myopathy 4

Similar variants

LDB3 p.Ser347Ala 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-ser347 (accessed [today's date]).

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