Is LDB3 p.Thr91= (c.273G>A) pathogenic?

LDB3 p.Thr91= (c.273G>A) is classified Benign/Likely benign in LDB3 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-25). Low-frequency (popmax 1.91%, sas); Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Thr91= (c.273G>A)?

LDB3 p.Thr91= (c.273G>A) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1C, myofibrillar myopathy 4 (ClinVar).

How common is LDB3 p.Thr91= (c.273G>A) in the general population?

LDB3 p.Thr91= (c.273G>A) is low-frequency (popmax 1.91%, sas) (gnomAD).

LDB3 p.Thr91=

c.273G>A · rs45613039 · VCV45542

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.91%, sas)

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 -2.1	GERP -4.1
Overall
CADD	4.466	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.91% South Asian · 1,742/91,066 alleles

Filtering AF 1.84% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.81%

Overall 0.118% 1,898/1,614,110 alleles · low-frequency exomes 1,792/1,461,850 · genomes 106/152,260 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	1.91%	52
Remaining individualsnot grpmax-eligible	0.126%	791
Middle Eastern	0.033%	3,031
Admixed American	0.00833%	12,005
African / African-American	0.00666%	15,009
European (non-Finnish)	0.00551%	18,154

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.Thr91=
Coding: c.273G>A
MANE Select: NM_007078
dbSNP: rs45613039
Type: single nucleotide variant
Location: chr10:86680109 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 91: 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.Thr91Met 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-thr91 (accessed [today's date]).

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