Is LDB3 p.Arg516= (c.1548G>A) pathogenic?

LDB3 p.Arg516= (c.1548G>A) is classified Likely benign in LDB3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-08). Very rare (popmax 0.00203%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with LDB3 p.Arg516= (c.1548G>A)?

LDB3 p.Arg516= (c.1548G>A) is associated with Cardiovascular phenotype, myofibrillar myopathy 4 (ClinVar).

How common is LDB3 p.Arg516= (c.1548G>A) in the general population?

LDB3 p.Arg516= (c.1548G>A) is very rare (popmax 0.00203%, nfe) (gnomAD).

LDB3 p.Arg516=

c.1548G>A · rs376826874 · VCV1148507

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00203%, 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 0.91	GERP 0.73, phastCons 1
Overall
CADD	1.113	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00203% European (non-Finnish) · 24/1,179,886 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00149% 24/1,613,618 alleles · very rare exomes 21/1,461,830 · genomes 3/151,788 · joint denominator

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.Arg516=
Coding: c.1548G>A
MANE Select: NM_007078
dbSNP: rs376826874
Type: single nucleotide variant
Location: chr10:86716643 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 516: a modified residue (omega-n-methylarginine); 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: myofibrillar myopathy 4

Similar variants

LDB3 p.Arg516Trp Uncertain significance ★★ ⚠ same residue
LDB3 p.Arg516Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
LDB3 p.Arg516Leu 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

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-arg516 (accessed [today's date]).

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