Is CUL3 p.Ser96Ter (c.287C>G) pathogenic?

CUL3 p.Ser96Ter (c.287C>G) is classified Likely pathogenic in CUL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-29). Absent from gnomAD v4.1; Associated with neurodevelopmental disorder with or without autism or seizures.

What condition is associated with CUL3 p.Ser96Ter (c.287C>G)?

CUL3 p.Ser96Ter (c.287C>G) is associated with neurodevelopmental disorder with or without autism or seizures (ClinVar).

How common is CUL3 p.Ser96Ter (c.287C>G) in the general population?

CUL3 p.Ser96Ter (c.287C>G) is absent from gnomAD v4.1 (gnomAD).

CUL3 p.Ser96Ter

c.287C>G · rs2106264503 · VCV3065699

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 3 of 16
REVEL	0.46	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CUL3
Protein: p.Ser96Ter
Coding: c.287C>G
MANE Select: NM_003590
dbSNP: rs2106264503
Type: single nucleotide variant
Location: chr2:224535619 (GRCh38)
Gene constraint: LOEUF 0.365 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.68 · 31 PDB

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 c.883+1G>T Pathogenic ★★ same condition
CUL3 p.Arg128Cys Pathogenic/Likely pathogenic ★★ same condition
CUL3 p.Arg148Ter Pathogenic ★★ same condition
CUL3 p.Arg247Ter Pathogenic ★★ same condition
CUL3 p.Gln641Ter Pathogenic ★★ same condition
CUL3 p.Gly143Ter Likely pathogenic ★★ same condition
CUL3 c.1377+6G>T Uncertain significance ★★ same condition
CUL3 c.884-5T>A Uncertain significance ★★ 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-ser96ter (accessed [today's date]).

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