Is CUL3 p.Asp413Val (c.1238A>T) pathogenic?

CUL3 p.Asp413Val (c.1238A>T) is classified Uncertain significance in CUL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: likely pathogenic (0.9893); Absent from gnomAD v4.1.

How common is CUL3 p.Asp413Val (c.1238A>T) in the general population?

CUL3 p.Asp413Val (c.1238A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CUL3 p.Asp413Val (c.1238A>T)?

AlphaMissense predicts likely pathogenic (score 0.9893) — an in-silico prediction, not a clinical call.

CUL3 p.Asp413Val

c.1238A>T · VCV4747300

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9893 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9893	likely pathogenic
REVEL	0.848	moderately pathogenic-leaning
SaProt	LLR -14.58	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.24	acceptor gain · deltas
Pangolin	Δ0.31	gain · loss 0.20 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.2	GERP 2.7, phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 76 kb · p 5e-41 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Asp413Val
Coding: c.1238A>T
MANE Select: NM_003590
Type: single nucleotide variant
Location: chr2:224503791 (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

Similar variants

CUL3 p.Asp413Gly Likely pathogenic ★ same residue
CUL3 p.Asp413fs Pathogenic same residue
CUL3 c.1377+1G>A Pathogenic/Likely pathogenic ★★ same type
CUL3 c.1377+4A>G Likely pathogenic ★★ same type
CUL3 c.883+1G>A Pathogenic/Likely pathogenic ★★ same type
CUL3 c.883+1G>T Pathogenic ★★ same type
CUL3 p.Arg128Cys Pathogenic/Likely pathogenic ★★ same type
CUL3 p.Arg148Ter Pathogenic ★★ 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/cul3-p-asp413val (accessed [today's date]).

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