Is CUL3 p.Val129fs (c.385_388del) pathogenic?

CUL3 p.Val129fs (c.385388del) is classified Likely pathogenic in CUL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). Associated with neurodevelopmental disorder with or without autism or seizures.

What condition is associated with CUL3 p.Val129fs (c.385_388del)?

CUL3 p.Val129fs (c.385_388del) is associated with neurodevelopmental disorder with or without autism or seizures (ClinVar).

CUL3 p.Val129fs

c.385_388del · VCV4855560

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

neurodevelopmental disorder with or without autism or seizures

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 4 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.9, phastCons 1

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

Variant & gene context

Gene: CUL3
Protein: p.Val129fs
Coding: c.385_388del
MANE Select: NM_003590
Type: Microsatellite
Location: chr2:224514763 (GRCh38)
Gene constraint: LOEUF 0.365 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.68 · 31 PDB
Residue 129: an α-helix

Full CUL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder with or without autism or seizures — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CUL3 p.Asp449_Ser450insTer Pathogenic/Likely pathogenic ★★ same condition
CUL3 p.Leu165fs Pathogenic/Likely pathogenic ★★ same condition
CUL3 p.Ser517fs Pathogenic/Likely pathogenic ★★ same condition
CUL3 p.His543fs Likely pathogenic ★ same condition
CUL3 c.2176-9_2176-6del Uncertain significance ★ same condition
CUL3 p.Val129= Likely benign ★ same residue
CUL3 c.883+1G>T Pathogenic ★★ same condition
CUL3 p.Arg128Cys Pathogenic/Likely 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/cul3-p-val129fs (accessed [today's date]).

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