Is LDB3 p.Ala331= (c.993G>A) pathogenic?

LDB3 p.Ala331= (c.993G>A) is classified Benign/Likely benign in LDB3 (ClinVar, Multiple submitters, 18 submitters; last evaluated 2026-04-01). Rare (popmax 0.16%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Ala331= (c.993G>A)?

LDB3 p.Ala331= (c.993G>A) is associated with Cardiovascular phenotype, cardiomyopathy, myofibrillar myopathy 4 (ClinVar).

How common is LDB3 p.Ala331= (c.993G>A) in the general population?

LDB3 p.Ala331= (c.993G>A) is rare (popmax 0.16%, nfe) (gnomAD).

LDB3 p.Ala331=

c.993G>A · rs140347820 · VCV45561

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 18 submitters

gnomAD v4.1

Rare

rare (popmax 0.16%, nfe)

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 -0.4	GERP -4.3
Overall
CADD	1.567	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.16% European (non-Finnish) · 1,883/1,179,956 alleles

Filtering AF 0.154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.151%

Overall 0.128% 2,065/1,613,018 alleles · rare exomes 1,930/1,460,844 · genomes 135/152,174 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.16%	627
Finnishnot grpmax-eligible	0.128%	780
Amishnot grpmax-eligible	0.11%	912
Remaining individualsnot grpmax-eligible	0.107%	932
African / African-American	0.0307%	3,257
Admixed American	0.015%	6,666
South Asian	0.0011%	91,078

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.Ala331=
Coding: c.993G>A
MANE Select: NM_007078
dbSNP: rs140347820
Type: single nucleotide variant
Location: chr10:86706627 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 331: 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.Ala331Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
LDB3 p.Ala331Val Conflicting classifications of pathogenicity ★ ⚠ 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-ala331 (accessed [today's date]).

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