Is LDB3 p.Ser474= (c.1422G>A) pathogenic?

LDB3 p.Ser474= (c.1422G>A) is classified Benign/Likely benign in LDB3 (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-05-01). Rare (popmax 0.292%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Ser474= (c.1422G>A)?

LDB3 p.Ser474= (c.1422G>A) is associated with Cardiovascular phenotype, cardiomyopathy, myofibrillar myopathy 4 (ClinVar).

How common is LDB3 p.Ser474= (c.1422G>A) in the general population?

LDB3 p.Ser474= (c.1422G>A) is rare (popmax 0.292%, nfe) (gnomAD).

LDB3 p.Ser474=

c.1422G>A · rs142625982 · VCV36444

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

gnomAD v4.1

Rare

rare (popmax 0.292%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.46	acceptor gain · deltas
Pangolin	Δ0.36	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -10	GERP -2.5
Overall
CADD	4.679	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.292% European (non-Finnish) · 3,444/1,179,244 alleles

Filtering AF 0.284% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.281%

Overall 0.235% 3,789/1,610,926 alleles · rare exomes 3,581/1,461,666 · genomes 208/149,260 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.292%	342
Remaining individualsnot grpmax-eligible	0.261%	383
Finnishnot grpmax-eligible	0.0849%	1,178
South Asian	0.066%	1,515
African / African-American	0.0568%	1,760
Admixed American	0.0352%	2,839
Middle Eastern	0.0165%	6,052
East Asian	0.00671%	14,893
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,578

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.Ser474=
Coding: c.1422G>A
MANE Select: NM_007078
dbSNP: rs142625982
Type: single nucleotide variant
Location: chr10:86716517 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 474: 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 myofibrillar myopathy 4

Similar variants

LDB3 p.Ser474Leu Uncertain significance ★★ ⚠ same residue
LDB3 p.Ser474Pro 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-ser474 (accessed [today's date]).

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