Is LDB3 p.Arg533fs (c.1597del) pathogenic?

LDB3 p.Arg533fs (c.1597del) is classified Conflicting classifications of pathogenicity in LDB3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-19). Very rare (popmax 8.47e-05%, nfe).

How common is LDB3 p.Arg533fs (c.1597del) in the general population?

LDB3 p.Arg533fs (c.1597del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

LDB3 p.Arg533fs

c.1597del · rs2492810461 · VCV2504036

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.1	GERP 0.97, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,982 alleles

Overall 6.2e-05% 1/1,613,866 alleles · very rare exomes 1/1,461,634 · genomes 0/152,232 · 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.Arg533fs
Coding: c.1597del
MANE Select: NM_007078
dbSNP: rs2492810461
Type: Deletion
Location: chr10:86716692 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 533: a modified residue (omega-n-methylarginine)

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

Similar variants

LDB3 p.Arg533Met Uncertain significance ★ same residue
LDB3 p.Arg533Ser Uncertain significance ★ ⚠ same residue
LDB3 c.860-22_860-12del Uncertain significance ★★ same type
LDB3 p.Glu483_Ala485del Uncertain significance ★★ same type
LDB3 p.Val676fs Uncertain significance ★★ same type
LDB3 p.Ala434_Pro449del Benign ★★ same type
LDB3 c.1086-247_1231+2del Pathogenic ★ same type
LDB3 p.Ala319fs Likely pathogenic ★ same type

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-arg533fs (accessed [today's date]).

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