Is CUL4B p.Arg878= (c.2634G>A) pathogenic?

CUL4B p.Arg878= (c.2634G>A) is classified Benign/Likely benign in CUL4B (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-24). Low-frequency (popmax 1.31%, afr); Associated with Inborn genetic diseases.

What condition is associated with CUL4B p.Arg878= (c.2634G>A)?

CUL4B p.Arg878= (c.2634G>A) is associated with Inborn genetic diseases, X-linked intellectual disability, Cabezas type (ClinVar).

How common is CUL4B p.Arg878= (c.2634G>A) in the general population?

CUL4B p.Arg878= (c.2634G>A) is low-frequency (popmax 1.31%, afr) (gnomAD).

CUL4B p.Arg878=

c.2634G>A · rs143580749 · VCV506496

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.31%, afr)

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 0.38	phastCons 0.99
Overall
CADD	4.957	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.31% African / African-American · 746/56,855 alleles

Filtering AF 1.23% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2%

Overall 0.0682% 815/1,195,173 alleles · low-frequency exomes 414/1,083,397 · genomes 401/111,776 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.31%	76
Remaining individualsnot grpmax-eligible	0.0854%	1,171
Admixed American	0.0528%	1,893
South Asian	0.00354%	28,245
European (non-Finnish)	0.000339%	294,794

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.Arg878=
Coding: c.2634G>A
MANE Select: NM_001079872
dbSNP: rs143580749
Type: single nucleotide variant
Location: chrX:120526815 (GRCh38)
Structure: AlphaFold pLDDT 80.02 · 5 PDB
Residue 878: the cullin neddylation domain

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.Arg878Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
CUL4B p.Arg878Trp 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

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-arg878 (accessed [today's date]).

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