Is CUL4B p.Asp633= (c.1899C>T) pathogenic?

CUL4B p.Asp633= (c.1899C>T) is classified Benign in CUL4B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). Ultra-rare (popmax 0.0885%, sas); Associated with X-linked intellectual disability, Cabezas type.

What condition is associated with CUL4B p.Asp633= (c.1899C>T)?

CUL4B p.Asp633= (c.1899C>T) is associated with X-linked intellectual disability, Cabezas type (ClinVar).

How common is CUL4B p.Asp633= (c.1899C>T) in the general population?

CUL4B p.Asp633= (c.1899C>T) is ultra-rare (popmax 0.0885%, sas) (gnomAD).

CUL4B p.Asp633=

c.1899C>T · VCV4738574

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0885%, sas)

Conditions

X-linked intellectual disability, Cabezas type

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 3.1	GERP 0.4, phastCons 1
Overall
CADD	8.112	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0885% South Asian · 50/56,521 alleles

Filtering AF 0.0689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.062%

Overall 0.00458% 55/1,201,334 alleles · ultra-rare exomes 50/1,089,434 · genomes 5/111,900 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0885%	1,130
Remaining individualsnot grpmax-eligible	0.00846%	11,820
African / African-American	0.00175%	57,131

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.Asp633=
Coding: c.1899C>T
MANE Select: NM_001079872
Type: single nucleotide variant
Location: chrX:120538163 (GRCh38)
Structure: AlphaFold pLDDT 80.02 · 5 PDB

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

Disease context

X-linked intellectual disability, Cabezas type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CUL4B p.Asp633Glu Uncertain significance ★ ⚠ same residue
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

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-asp633 (accessed [today's date]).

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