Is LDB3 p.Ala482= (c.1446G>A) pathogenic?

LDB3 p.Ala482= (c.1446G>A) is classified Conflicting classifications of pathogenicity in LDB3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-14). Very rare (popmax 0.00669%, eas); Associated with myofibrillar myopathy 4.

What condition is associated with LDB3 p.Ala482= (c.1446G>A)?

LDB3 p.Ala482= (c.1446G>A) is associated with myofibrillar myopathy 4 (ClinVar).

How common is LDB3 p.Ala482= (c.1446G>A) in the general population?

LDB3 p.Ala482= (c.1446G>A) is very rare (popmax 0.00669%, eas) (gnomAD).

LDB3 p.Ala482=

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.1446G>A · rs745655908 · VCV1054802

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Conditions

myofibrillar myopathy 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -7.8	GERP -3.5
Overall
CADD	0.179	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,810 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000868% 14/1,613,056 alleles · very rare exomes 13/1,461,808 · genomes 1/151,248 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,937
African / African-American	0.00402%	24,859
Admixed American	0.00334%	29,941
South Asian	0.0011%	91,032
European (non-Finnish)	0.000424%	235,961

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.Ala482=
Coding: c.1446G>A
MANE Select: NM_007078
dbSNP: rs745655908
Type: single nucleotide variant
Location: chr10:86716541 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 482: 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.Ala482Gly Uncertain significance ★★ ⚠ same residue
LDB3 p.Ala482Val Conflicting classifications of pathogenicity ★ ⚠ same residue
LDB3 p.Ala482fs Pathogenic ★ 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-ala482 (accessed [today's date]).

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