LDB3 p.Ala305=
c.915G>A · rs753526743 · VCV626500
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00769%, sas)
Conditions
2
cardiomyopathy
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 1.6 | GERP -3, phastCons 1 |
| Overall | ||
| CADD | 9.976 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00769%
South Asian · 7/91,078 alleles
Filtering AF
0.00359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00255%
Overall
0.000682%
11/1,612,546 alleles · very rare
exomes 10/1,460,420 · genomes 1/152,126 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00769% | 13,011 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,821 |
| European (non-Finnish) | 8.47e-05% | 1,179,976 |
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.Ala305=
- Coding
- c.915G>A
- MANE Select
- NM_007078
- dbSNP
- rs753526743
- Type
- single nucleotide variant
- Location
- chr10:86706549 (GRCh38)
- Gene constraint
- LOEUF 0.864 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 61.98 · 2 PDB
- Residue 305
- the 'disordered' region
Similar variants
- LDB3 p.Ala305Glu Uncertain significance ★★ ⚠ same residue
- LDB3 p.Ala305Pro Uncertain significance ★★ ⚠ same residue
- LDB3 p.Ala305Val Uncertain significance ★★ ⚠ same residue
- LDB3 p.Ala305Ser 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
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-ala305 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown