Is LDB3 p.Pro433= (c.1299T>A) pathogenic?

LDB3 p.Pro433= (c.1299T>A) is classified Likely benign in LDB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-20). Rare (popmax 0.176%, eas); Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Pro433= (c.1299T>A)?

LDB3 p.Pro433= (c.1299T>A) is associated with Cardiovascular phenotype (ClinVar).

How common is LDB3 p.Pro433= (c.1299T>A) in the general population?

LDB3 p.Pro433= (c.1299T>A) is rare (popmax 0.176%, eas) (gnomAD).

LDB3 p.Pro433=

c.1299T>A · rs761685061 · VCV1769291

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.176%, eas)

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 -0.092	GERP -1.5, phastCons 0.94
Overall
CADD	1.086	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.176% East Asian · 23/13,074 alleles

Filtering AF 0.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.102%

Overall 0.0571% 394/689,780 alleles · rare exomes 386/673,914 · genomes 8/15,866 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.176%	568
Remaining individualsnot grpmax-eligible	0.119%	838
Ashkenazi Jewishnot grpmax-eligible	0.104%	958
African / African-American	0.1%	996
Finnishnot grpmax-eligible	0.059%	1,696
Admixed American	0.0576%	1,735
European (non-Finnish)	0.0521%	1,920
South Asian	0.008%	12,502

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.Pro433=
Coding: c.1299T>A
MANE Select: NM_007078
dbSNP: rs761685061
Type: single nucleotide variant
Location: chr10:86716394 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 433: 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

Similar variants

LDB3 p.Pro433Leu Uncertain significance ★★ ⚠ same residue
LDB3 p.Pro433Ala Uncertain significance ★ ⚠ same residue
LDB3 p.Pro433Thr Uncertain significance ★ ⚠ same residue
LDB3 c.246-3C>T Uncertain significance ★★ same condition
LDB3 c.860-3C>T Uncertain significance ★★ same condition
LDB3 p.Ala119Val Uncertain significance ★★ ⚠ same condition
LDB3 p.Ala126Val Uncertain significance ★★ ⚠ same condition
LDB3 p.Ala248Thr 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-pro433 (accessed [today's date]).

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