Is LDB1 p.Ala136fs (c.404dup) pathogenic?

LDB1 p.Ala136fs (c.404dup) is classified Pathogenic in LDB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-23). Associated with autosomal dominant non-syndromic intellectual disability.

What condition is associated with LDB1 p.Ala136fs (c.404dup)?

LDB1 p.Ala136fs (c.404dup) is associated with autosomal dominant non-syndromic intellectual disability (ClinVar).

LDB1 p.Ala136fs

c.404dup · VCV4818732

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

autosomal dominant non-syndromic intellectual disability

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 6 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.7	GERP -1.7, phastCons 1

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

Variant & gene context

Gene: LDB1
Protein: p.Ala136fs
Coding: c.404dup
MANE Select: NM_001113407
Type: Duplication
Location: chr10:102110649 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.04 · 9 PDB
Residue 136: a β-strand

Full LDB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant non-syndromic intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LDB1 p.Arg121Trp Likely pathogenic ★ same condition
LDB1 p.Arg193Trp Likely pathogenic ★ same condition
LDB1 p.Arg356fs Pathogenic ★ same condition
LDB1 p.Gln203Ter Likely pathogenic ★ same condition
LDB1 p.Gln333Ter Pathogenic ★ same condition
LDB1 p.Gln66Ter Pathogenic ★ same condition
LDB1 p.Glu349fs Pathogenic ★ same condition
LDB1 p.Ser317fs Pathogenic ★ 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/ldb1-p-ala136fs (accessed [today's date]).

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