Is LDB3 p.Ile158= (c.474C>T) pathogenic?

LDB3 p.Ile158= (c.474C>T) is classified Likely benign in LDB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-27). Very rare (popmax 8.47e-05%, nfe).

How common is LDB3 p.Ile158= (c.474C>T) in the general population?

LDB3 p.Ile158= (c.474C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

LDB3 p.Ile158=

c.474C>T · VCV4908466

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 2.1, phastCons 1
Overall
CADD	20.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,046 alleles

Overall 6.19e-05% 1/1,614,254 alleles · very rare exomes 1/1,461,884 · genomes 0/152,370 · 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.Ile158=
Coding: c.474C>T
MANE Select: NM_007078 · reported on NM_001368067
Type: single nucleotide variant
Location: chr10:86687198 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.98 · 2 PDB
Residue 158: the 'disordered' region

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

Similar variants

LDB3 p.Ala158Ser Uncertain significance ★ ⚠ same residue
LDB3 p.Ala158Val Uncertain significance ★ ⚠ same residue
LDB3 p.Ile158Val Uncertain significance ★ same residue
LDB3 p.Ala147Thr Pathogenic/Likely pathogenic ★★ same type
LDB3 p.Ala165Val Pathogenic/Likely pathogenic ★★ same type
LDB3 c.1231+4A>C Uncertain significance ★★ same type
LDB3 c.1858-11C>A Uncertain significance ★★ same type
LDB3 c.246-3C>T Uncertain significance ★★ 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-ile158 (accessed [today's date]).

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