Is CUL4B p.Val599= (c.1797C>T) pathogenic?

CUL4B p.Val599= (c.1797C>T) is classified Benign/Likely benign in CUL4B (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-26). Rare (popmax 0.294%, sas); Associated with Inborn genetic diseases.

What condition is associated with CUL4B p.Val599= (c.1797C>T)?

CUL4B p.Val599= (c.1797C>T) is associated with Inborn genetic diseases, X-linked intellectual disability, Cabezas type (ClinVar).

How common is CUL4B p.Val599= (c.1797C>T) in the general population?

CUL4B p.Val599= (c.1797C>T) is rare (popmax 0.294%, sas) (gnomAD).

CUL4B p.Val599=

c.1797C>T · rs751833365 · VCV1239584

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.294%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP -1.2, phastCons 1
Overall
CADD	3.104	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.294% South Asian · 167/56,746 alleles

Filtering AF 0.258% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.244%

Overall 0.0167% 201/1,206,861 alleles · rare exomes 186/1,094,893 · genomes 15/111,968 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.294%	340
Middle Eastern	0.069%	1,448
Remaining individualsnot grpmax-eligible	0.0126%	7,918
Admixed American	0.00875%	11,428
European (non-Finnish)	0.00235%	42,509

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CUL4B
Protein: p.Val599=
Coding: c.1797C>T
MANE Select: NM_001079872
dbSNP: rs751833365
Type: single nucleotide variant
Location: chrX:120538715 (GRCh38)
Structure: AlphaFold pLDDT 80.02 · 5 PDB

Full CUL4B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: X-linked intellectual disability, Cabezas type

Similar variants

CUL4B p.Arg351Ter Likely pathogenic ★★ same condition
CUL4B p.Arg370Ter Pathogenic ★★ same condition
CUL4B p.Gln241Ter Pathogenic ★★ same condition
CUL4B p.Thr813= Pathogenic/Likely pathogenic ★★ same condition
CUL4B c.2592+3A>T Uncertain significance ★★ same condition
CUL4B c.777-3C>T Uncertain significance ★★ same condition
CUL4B p.Ala16Pro Uncertain significance ★★ ⚠ same condition
CUL4B p.Cys712Arg 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/cul4b-p-val599 (accessed [today's date]).

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