Is LDB3 p.Ser203= (c.609G>A) pathogenic?

LDB3 p.Ser203= (c.609G>A) is classified Benign in LDB3 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-02). Common (popmax 5.12%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Ser203= (c.609G>A)?

LDB3 p.Ser203= (c.609G>A) is associated with Cardiovascular phenotype, cardiomyopathy, myofibrillar myopathy 4 (ClinVar).

LDB3 p.Ser203=

Q: How common is LDB3 p.Ser203= (c.609G>A) in the general population?

LDB3 p.Ser203= (c.609G>A) is common (popmax 5.12%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.609G>A · rs45531131 · VCV45550

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 5.12%, 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/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.24	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -4.4	GERP -4.1
Overall
CADD	12.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.12% African / African-American · 3,838/74,962 alleles

Filtering AF 4.98% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.93%

Overall 0.273% 4,397/1,611,658 alleles · common exomes 2,214/1,459,310 · genomes 2,183/152,348 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.12%	20
Remaining individualsnot grpmax-eligible	0.326%	307
Admixed American	0.236%	424
Middle Eastern	0.149%	673
European (non-Finnish)	0.0169%	5,923
South Asian	0.0066%	15,150
Finnishnot grpmax-eligible	0.00157%	63,620

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.Ser203=
Coding: c.609G>A
MANE Select: NM_007078
dbSNP: rs45531131
Type: single nucleotide variant
Location: chr10:86681723 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB

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.Ser203Leu Uncertain significance ★★ ⚠ same residue
LDB3 p.Ser203Trp 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

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-ser203 (accessed [today's date]).

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