Is CDC42BPG p.Arg1029Lys (c.3086G>A) pathogenic?

CDC42BPG p.Arg1029Lys (c.3086G>A) is classified Uncertain significance in CDC42BPG (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.2117); Ultra-rare (popmax 0.0495%, mid).

How common is CDC42BPG p.Arg1029Lys (c.3086G>A) in the general population?

CDC42BPG p.Arg1029Lys (c.3086G>A) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

What do computational predictors say about CDC42BPG p.Arg1029Lys (c.3086G>A)?

AlphaMissense predicts likely benign (score 0.2117) — an in-silico prediction, not a clinical call.

CDC42BPG p.Arg1029Lys

c.3086G>A · rs566738886 · VCV2251919

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2117 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2117	likely benign
REVEL	0.382	indeterminate
SaProt	LLR -9.03	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 4.9	GERP -0.54, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 17 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	24.8	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 0.0495% Middle Eastern · 3/6,062 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00718%

Overall 0.000744% 12/1,613,662 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,021
Remaining individualsnot grpmax-eligible	0.0032%	31,250
South Asian	0.0011%	90,924
European (non-Finnish)	0.000509%	196,639

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.Arg1029Lys
Coding: c.3086G>A
MANE Select: NM_017525
dbSNP: rs566738886
Type: single nucleotide variant
Location: chr11:64832429 (GRCh38)
Gene constraint: LOEUF 1.039 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.90
Residue 1029: the ph domain

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-arg1029lys (accessed [today's date]).

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