Is CUL4B p.Arg554Cys (c.1660C>T) pathogenic?

CUL4B p.Arg554Cys (c.1660C>T) is classified Pathogenic in CUL4B (ClinVar, Single submitter, 2 submitters; last evaluated 2024-03-07). AlphaMissense: likely pathogenic (0.9967); No allele count reported in gnomAD v4.1 (AN 1,191,464); Associated with X-linked intellectual disability, Cabezas type.

What condition is associated with CUL4B p.Arg554Cys (c.1660C>T)?

CUL4B p.Arg554Cys (c.1660C>T) is associated with X-linked intellectual disability, Cabezas type (ClinVar).

How common is CUL4B p.Arg554Cys (c.1660C>T) in the general population?

CUL4B p.Arg554Cys (c.1660C>T) is no allele count reported in gnomAD v4.1 (AN 1,191,464) (gnomAD).

What do computational predictors say about CUL4B p.Arg554Cys (c.1660C>T)?

AlphaMissense predicts likely pathogenic (score 0.9967) — an in-silico prediction, not a clinical call.

CUL4B p.Arg554Cys

c.1660C>T · rs121434615 · VCV11338

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9967 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,191,464)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked intellectual disability, Cabezas type

Computational evidence

Protein change
AlphaMissense	0.9967	likely pathogenic ✓ concordant with ClinVar
REVEL	0.912	moderately pathogenic-leaning
SaProt	LLR -15.85	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.9, phastCons 1
Regional constraint	o/e 0.33	constrained · MANE · 14 kb · p 8.5e-31 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R572C vs ClinVar R554C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,191,464). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CUL4B
Protein: p.Arg554Cys
Coding: c.1660C>T
MANE Select: NM_001079872
dbSNP: rs121434615
Type: single nucleotide variant
Location: chrX:120539349 (GRCh38)
Structure: AlphaFold pLDDT 80.02 · 5 PDB
Residue 572 UniProt numbering: a UniProt-annotated variant site (in mrxsc)

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-arg554cys (accessed [today's date]).

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