Is CUL3 p.Asp413fs (c.1239del) pathogenic?

CUL3 p.Asp413fs (c.1239del) is classified Pathogenic in CUL3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-03-24). Absent from gnomAD; Associated with NEURODEVELOPMENTAL DISORDER WITHOUT AUTISM OR SEIZURES.

What condition is associated with CUL3 p.Asp413fs (c.1239del)?

CUL3 p.Asp413fs (c.1239del) is associated with NEURODEVELOPMENTAL DISORDER WITHOUT AUTISM OR SEIZURES (ClinVar).

How common is CUL3 p.Asp413fs (c.1239del) in the general population?

CUL3 p.Asp413fs (c.1239del) is absent from gnomAD (gnomAD).

CUL3 p.Asp413fs

c.1239del · rs1692487571 · VCV1048104

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

NEURODEVELOPMENTAL DISORDER 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 9 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.7, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CUL3
Protein: p.Asp413fs
Coding: c.1239del
MANE Select: NM_003590
dbSNP: rs1692487571
Type: Deletion
Location: chr2:224503790 (GRCh38)
Gene constraint: LOEUF 0.365 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.68 · 31 PDB
Residue 413: a UniProt-annotated variant site (in pha2e)

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

Disease context

NEURODEVELOPMENTAL DISORDER WITHOUT AUTISM OR SEIZURES

Similar variants

CUL3 p.Asp413Gly Likely pathogenic ★ same residue
CUL3 p.Asp413Val Uncertain significance ★ ⚠ same residue
CUL3 p.Arg46fs Pathogenic same condition
CUL3 p.Asn134fs Likely pathogenic same condition
CUL3 c.1377+1G>A Pathogenic/Likely pathogenic ★★ same condition
CUL3 c.540_541del Pathogenic/Likely pathogenic ★★ same condition
CUL3 p.Arg438Gly Pathogenic ★★ same condition
CUL3 p.Gln368fs 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-asp413fs (accessed [today's date]).

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