Is LDB3 p.Ser182Arg (c.544A>C) pathogenic?

LDB3 p.Ser182Arg (c.544A>C) is classified Uncertain significance in LDB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-17). Very rare (popmax 6.2e-05%); Associated with myofibrillar myopathy 4.

What condition is associated with LDB3 p.Ser182Arg (c.544A>C)?

LDB3 p.Ser182Arg (c.544A>C) is associated with myofibrillar myopathy 4 (ClinVar).

How common is LDB3 p.Ser182Arg (c.544A>C) in the general population?

LDB3 p.Ser182Arg (c.544A>C) is very rare (popmax 6.2e-05%) (gnomAD).

LDB3 p.Ser182Arg

Q: How is Late-onset distal myopathy, Markesbery-Griggs type inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.544A>C · VCV3614252

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Conditions

myofibrillar myopathy 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.311	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.85 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 64 kb · p 0.14 · regional, not allelic
Overall
CADD	20.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,614,106 alleles · very rare exomes 1/1,461,806 · genomes 0/152,300 · 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.Ser182Arg
Coding: c.544A>C
MANE Select: NM_007078 · reported on NM_001368067
Type: single nucleotide variant
Location: chr10:86687268 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 182: the 'disordered' region

Full LDB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

myofibrillar myopathy 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Late-onset distal myopathy, Markesbery-Griggs type (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

LDB3 p.Gly182Asp Uncertain significance ★★ ⚠ same residue
LDB3 p.Ser182= Benign ★★ same residue
LDB3 p.Gly182Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
LDB3 p.Ser182Cys Uncertain significance ★ same residue
LDB3 p.Gly182= Likely benign ★ 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

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-ser182arg (accessed [today's date]).

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