Is CUL4B p.Phe693Val (c.2077T>G) pathogenic?

CUL4B p.Phe693Val (c.2077T>G) is classified Uncertain significance in CUL4B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-13). AlphaMissense: likely pathogenic (0.9872); Absent from gnomAD v4.1.

How common is CUL4B p.Phe693Val (c.2077T>G) in the general population?

CUL4B p.Phe693Val (c.2077T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CUL4B p.Phe693Val (c.2077T>G)?

AlphaMissense predicts likely pathogenic (score 0.9872) — an in-silico prediction, not a clinical call.

CUL4B p.Phe693Val

c.2077T>G · VCV4952575

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9872 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9872	likely pathogenic
REVEL	0.874	moderately pathogenic-leaning
SaProt	LLR -14.48	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 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.33	constrained · MANE · 14 kb · p 8.5e-31 · regional, not allelic
Overall
CADD	27.1	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 F711V vs ClinVar F693V) — 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.Phe693Val
Coding: c.2077T>G
MANE Select: NM_001079872
Type: single nucleotide variant
Location: chrX:120535913 (GRCh38)
Structure: AlphaFold pLDDT 80.02 · 5 PDB

Full CUL4B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CUL4B p.Arg351Ter Likely pathogenic ★★ same type
CUL4B p.Arg370Ter Pathogenic ★★ same type
CUL4B p.Gln241Ter Pathogenic ★★ same type
CUL4B p.Thr813= Pathogenic/Likely pathogenic ★★ same type
CUL4B c.2592+3A>T Uncertain significance ★★ same type
CUL4B c.777-3C>T Uncertain significance ★★ same type
CUL4B p.Ala16Pro Uncertain significance ★★ ⚠ same type
CUL4B p.Cys712Arg Uncertain significance ★★ ⚠ same type

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-phe693val (accessed [today's date]).

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