Is CUL4B p.Ile271Phe (c.811A>T) pathogenic?

CUL4B p.Ile271Phe (c.811A>T) is classified Uncertain significance in CUL4B (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-12). AlphaMissense: likely pathogenic (0.5852); Absent from gnomAD v4.1; Associated with X-linked intellectual disability, Cabezas type.

What condition is associated with CUL4B p.Ile271Phe (c.811A>T)?

CUL4B p.Ile271Phe (c.811A>T) is associated with X-linked intellectual disability, Cabezas type (ClinVar).

How common is CUL4B p.Ile271Phe (c.811A>T) in the general population?

CUL4B p.Ile271Phe (c.811A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CUL4B p.Ile271Phe (c.811A>T)?

AlphaMissense predicts likely pathogenic (score 0.5852) — an in-silico prediction, not a clinical call.

CUL4B p.Ile271Phe

c.811A>T · rs2521133019 · VCV2708826

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5852 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

X-linked intellectual disability, Cabezas type

Computational evidence

Protein change
AlphaMissense	0.5852	likely pathogenic
REVEL	0.534	indeterminate
SaProt	LLR -11.30	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.21	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 6.2	GERP 2.2, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 17 kb · p 7.5e-08 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I289F vs ClinVar I271F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CUL4B
Protein: p.Ile271Phe
Coding: c.811A>T
MANE Select: NM_001079872
dbSNP: rs2521133019
Type: single nucleotide variant
Location: chrX:120546582 (GRCh38)
Structure: AlphaFold pLDDT 80.02 · 5 PDB
Residue 289 UniProt numbering: 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-ile271phe (accessed [today's date]).

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