Is CDC42BPB p.Ser464Pro (c.1390T>C) pathogenic?

CDC42BPB p.Ser464Pro (c.1390T>C) is classified Uncertain significance in CDC42BPB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely pathogenic (0.9642); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CDC42BPB p.Ser464Pro (c.1390T>C)?

CDC42BPB p.Ser464Pro (c.1390T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CDC42BPB p.Ser464Pro (c.1390T>C) in the general population?

CDC42BPB p.Ser464Pro (c.1390T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC42BPB p.Ser464Pro (c.1390T>C)?

AlphaMissense predicts likely pathogenic (score 0.9642) — an in-silico prediction, not a clinical call.

CDC42BPB p.Ser464Pro

c.1390T>C · VCV4608494

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9642 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9642	likely pathogenic
REVEL	0.298	indeterminate
SaProt	LLR -11.54	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP -0.017, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 8,980 bp · p 0.023 · regional, not allelic
Overall
CADD	22.2	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.

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: CDC42BPB
Protein: p.Ser464Pro
Coding: c.1390T>C
MANE Select: NM_006035
Type: single nucleotide variant
Location: chr14:102975801 (GRCh38)
Gene constraint: LOEUF 0.235 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 76.28 · 6 PDB
Residue 464: the 'disordered' region

Full CDC42BPB 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

Similar variants

CDC42BPB p.Ser464= Likely benign ★ same residue
CDC42BPB p.Asp1234Asn Uncertain significance ★★ same condition
CDC42BPB p.Asp503Val Uncertain significance ★★ ⚠ same condition
CDC42BPB p.His1304Tyr Uncertain significance ★★ same condition
CDC42BPB p.Ser44Leu Uncertain significance ★★ ⚠ same condition
CDC42BPB p.Val52Ala Uncertain significance ★★ ⚠ same condition
CDC42BPB p.Ala1532Val Likely benign ★★ same condition
CDC42BPB p.Arg1570= Likely benign ★★ 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/cdc42bpb-p-ser464pro (accessed [today's date]).

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