Is CDC42BPG p.Pro1430Arg (c.4289C>G) pathogenic?

CDC42BPG p.Pro1430Arg (c.4289C>G) is classified Uncertain significance in CDC42BPG (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-05). AlphaMissense: ambiguous (0.3904); Very rare (popmax 0.00415%, nfe).

How common is CDC42BPG p.Pro1430Arg (c.4289C>G) in the general population?

CDC42BPG p.Pro1430Arg (c.4289C>G) is very rare (popmax 0.00415%, nfe) (gnomAD).

What do computational predictors say about CDC42BPG p.Pro1430Arg (c.4289C>G)?

AlphaMissense predicts ambiguous (score 0.3904) — an in-silico prediction, not a clinical call.

CDC42BPG p.Pro1430Arg

c.4289C>G · rs150833954 · VCV2513205

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3904 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00415%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3904	ambiguous
REVEL	0.436	indeterminate
SaProt	LLR -5.15	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 3,214 bp · p 0.00049 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00415% European (non-Finnish) · 49/1,179,958 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.00415% 67/1,613,974 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0187%	5,335
Remaining individualsnot grpmax-eligible	0.0096%	10,414
European (non-Finnish)grpmax	0.00415%	24,081

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CDC42BPG
Protein: p.Pro1430Arg
Coding: c.4289C>G
MANE Select: NM_017525
dbSNP: rs150833954
Type: single nucleotide variant
Location: chr11:64827150 (GRCh38)
Gene constraint: LOEUF 1.039 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.90

Full CDC42BPG gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC42BPG p.Ile77= Benign ★★ same type
CDC42BPG p.Lys467Asn Benign ★★ same type
CDC42BPG p.Pro1257= Benign ★★ same type
CDC42BPG p.Ala1013Val Uncertain significance ★ ⚠ same type
CDC42BPG p.Ala1036Val Uncertain significance ★ ⚠ same type
CDC42BPG p.Ala1071Val Uncertain significance ★ ⚠ same type
CDC42BPG p.Ala1098Thr Uncertain significance ★ ⚠ same type
CDC42BPG p.Ala1242Val 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/cdc42bpg-p-pro1430arg (accessed [today's date]).

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