Is CUL4A p.Ile696Val (c.2086A>G) pathogenic?

CUL4A p.Ile696Val (c.2086A>G) is classified Uncertain significance in CUL4A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-02). AlphaMissense: likely benign (0.1021); Absent from gnomAD v4.1.

How common is CUL4A p.Ile696Val (c.2086A>G) in the general population?

CUL4A p.Ile696Val (c.2086A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CUL4A p.Ile696Val (c.2086A>G)?

AlphaMissense predicts likely benign (score 0.1021) — an in-silico prediction, not a clinical call.

CUL4A p.Ile696Val

c.2086A>G · VCV4008334

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1021 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1021	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -10.23	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.32	constrained · MANE · 5,705 bp · p 3.3e-10 · regional, not allelic
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

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: CUL4A
Protein: p.Ile696Val
Coding: c.2086A>G
MANE Select: NM_001008895
Type: single nucleotide variant
Location: chr13:113260661 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.26 · 20 PDB
Residue 696: the cullin neddylation domain; an α-helix

Full CUL4A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CUL4A p.Ala13Pro Uncertain significance ★ ⚠ same type
CUL4A p.Ala208Val Uncertain significance ★ ⚠ same type
CUL4A p.Ala486Thr Uncertain significance ★ same type
CUL4A p.Arg144Gly Uncertain significance ★ same type
CUL4A p.Arg385Gln Uncertain significance ★ ⚠ same type
CUL4A p.Arg49Gln Uncertain significance ★ ⚠ same type
CUL4A p.Arg80Lys Uncertain significance ★ ⚠ same type
CUL4A p.Asn603Ser Uncertain significance ★ ⚠ 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/cul4a-p-ile696val (accessed [today's date]).

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