Is CDC42BPB p.Pro1107Ala (c.3319C>G) pathogenic?

CDC42BPB p.Pro1107Ala (c.3319C>G) is classified Uncertain significance in CDC42BPB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-17). AlphaMissense: likely benign (0.2944); Very rare (popmax 0.00133%, afr).

How common is CDC42BPB p.Pro1107Ala (c.3319C>G) in the general population?

CDC42BPB p.Pro1107Ala (c.3319C>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CDC42BPB p.Pro1107Ala (c.3319C>G)?

AlphaMissense predicts likely benign (score 0.2944) — an in-silico prediction, not a clinical call.

CDC42BPB p.Pro1107Ala

c.3319C>G · VCV4525796

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2944 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2944	likely benign
REVEL	0.293	indeterminate
SaProt	LLR -7.17	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.73, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 15 kb · p 2e-15 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00133% African / African-American · 1/74,948 alleles

Overall 0.000657% 1/152,224 alleles · very rare

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: CDC42BPB
Protein: p.Pro1107Ala
Coding: c.3319C>G
MANE Select: NM_006035
Type: single nucleotide variant
Location: chr14:102949895 (GRCh38)
Gene constraint: LOEUF 0.235 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 76.28 · 6 PDB
Residue 1107: the ph domain; a UniProt-annotated variant site (in chocns)

Full CDC42BPB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC42BPB c.2726+1G>A Pathogenic/Likely pathogenic ★★ same type
CDC42BPB p.Ala177Val Likely pathogenic ★★ same type
CDC42BPB p.Arg122Ter Pathogenic/Likely pathogenic ★★ same type
CDC42BPB p.Arg867Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
CDC42BPB p.Arg876Pro Likely pathogenic ★★ ⚠ same type
CDC42BPB p.Asp175Tyr Likely pathogenic ★★ same type
CDC42BPB p.Ser1530Ter Likely pathogenic ★★ same type
CDC42BPB p.Arg509Ter 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/cdc42bpb-p-pro1107ala (accessed [today's date]).

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