Is LDB3 p.Glu205= (c.615G>A) pathogenic?

LDB3 p.Glu205= (c.615G>A) is classified Likely benign in LDB3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-06). Very rare (popmax 0.00894%, eas); Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Glu205= (c.615G>A)?

LDB3 p.Glu205= (c.615G>A) is associated with Cardiovascular phenotype, myofibrillar myopathy 4 (ClinVar).

How common is LDB3 p.Glu205= (c.615G>A) in the general population?

LDB3 p.Glu205= (c.615G>A) is very rare (popmax 0.00894%, eas) (gnomAD).

LDB3 p.Glu205=

c.615G>A · rs775061423 · VCV1751937

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00894%, eas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.4	GERP 2.1, phastCons 1
Overall
CADD	11.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00894% East Asian · 4/44,736 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000311% 5/1,608,556 alleles · very rare exomes 3/1,456,288 · genomes 2/152,268 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00894%	11,184
European (non-Finnish)	8.5e-05%	1,176,887

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.Glu205=
Coding: c.615G>A
MANE Select: NM_007078
dbSNP: rs775061423
Type: single nucleotide variant
Location: chr10:86681729 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB

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: myofibrillar myopathy 4

Similar variants

LDB3 p.Glu205Ala Uncertain significance ★ ⚠ same residue
LDB3 p.Glu205Asp 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-glu205 (accessed [today's date]).

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