Is CDC42BPG p.Arg117Pro (c.350G>C) pathogenic?

CDC42BPG p.Arg117Pro (c.350G>C) is classified Uncertain significance in CDC42BPG (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-17). AlphaMissense: likely pathogenic (0.8814); Very rare (popmax 0.0011%, sas).

How common is CDC42BPG p.Arg117Pro (c.350G>C) in the general population?

CDC42BPG p.Arg117Pro (c.350G>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CDC42BPG p.Arg117Pro (c.350G>C)?

AlphaMissense predicts likely pathogenic (score 0.8814) — an in-silico prediction, not a clinical call.

CDC42BPG p.Arg117Pro

c.350G>C · rs775326529 · VCV2308059

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8814 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8814	likely pathogenic
REVEL	0.631	indeterminate
SaProt	LLR -11.83	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.7	GERP 0.79, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 17 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	26.1	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,084 alleles

Overall 0.000124% 2/1,613,824 alleles · very rare exomes 2/1,461,480 · genomes 0/152,344 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,084
European (non-Finnish)	8.47e-05%	1,180,016

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.Arg117Pro
Coding: c.350G>C
MANE Select: NM_017525
dbSNP: rs775326529
Type: single nucleotide variant
Location: chr11:64840635 (GRCh38)
Gene constraint: LOEUF 1.039 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.90
Residue 117: the protein kinase domain

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

Similar variants

CDC42BPG p.Arg117Leu Uncertain significance ★ same residue
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

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-arg117pro (accessed [today's date]).

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