Is CUL4B p.Ser264= (c.792C>T) pathogenic?

CUL4B p.Ser264= (c.792C>T) is classified Benign in CUL4B (ClinVar, Single submitter, 4 submitters; last evaluated 2025-03-27). Rare (popmax 0.115%, afr); Associated with X-linked intellectual disability, Cabezas type.

What condition is associated with CUL4B p.Ser264= (c.792C>T)?

CUL4B p.Ser264= (c.792C>T) is associated with X-linked intellectual disability, Cabezas type (ClinVar).

How common is CUL4B p.Ser264= (c.792C>T) in the general population?

CUL4B p.Ser264= (c.792C>T) is rare (popmax 0.115%, afr) (gnomAD).

CUL4B p.Ser264=

c.792C>T · rs201566181 · VCV1285197

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.115%, afr)

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	<0.2	all four deltas below 0.2 · G>C here scores Δ0.49 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7	GERP -1.6, phastCons 1
Overall
CADD	6.677	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.115% African / African-American · 65/56,556 alleles

Filtering AF 0.0924% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0843%

Overall 0.0064% 76/1,187,355 alleles · rare exomes 44/1,076,582 · genomes 32/110,773 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.115%	870
South Asian	0.00892%	11,217
Ashkenazi Jewishnot grpmax-eligible	0.00458%	21,829
Remaining individualsnot grpmax-eligible	0.00427%	23,417
European (non-Finnish)	0.000342%	291,989

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.Ser264=
Coding: c.792C>T
MANE Select: NM_001079872
dbSNP: rs201566181
Type: single nucleotide variant
Location: chrX:120546601 (GRCh38)
Structure: AlphaFold pLDDT 80.02 · 5 PDB
Residue 264: 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-ser264 (accessed [today's date]).

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