Is CUL4B p.Arg273= (c.819A>G) pathogenic?

CUL4B p.Arg273= (c.819A>G) is classified Benign in CUL4B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-27). Ultra-rare (popmax 0.0118%, eas); Associated with X-linked intellectual disability, Cabezas type.

What condition is associated with CUL4B p.Arg273= (c.819A>G)?

CUL4B p.Arg273= (c.819A>G) is associated with X-linked intellectual disability, Cabezas type (ClinVar).

How common is CUL4B p.Arg273= (c.819A>G) in the general population?

CUL4B p.Arg273= (c.819A>G) is ultra-rare (popmax 0.0118%, eas) (gnomAD).

CUL4B p.Arg273=

c.819A>G · rs778579288 · VCV2973993

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0118%, eas)

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
Pangolin	Δ0.22	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 4.1	GERP -0.097, phastCons 1
Overall
CADD	10.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0118% East Asian · 4/33,766 alleles

Filtering AF 0.00396% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.000415% 5/1,205,094 alleles · ultra-rare exomes 5/1,091,819 · genomes 0/113,275 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0118%	8,442
Remaining individualsnot grpmax-eligible	0.00211%	47,419

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.Arg273=
Coding: c.819A>G
MANE Select: NM_001079872
dbSNP: rs778579288
Type: single nucleotide variant
Location: chrX:120546574 (GRCh38)
Structure: AlphaFold pLDDT 80.02 · 5 PDB
Residue 273: an α-helix

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.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-arg273 (accessed [today's date]).

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