Is CDC42BPG p.Arg882Cys (c.2644C>T) pathogenic?

CDC42BPG p.Arg882Cys (c.2644C>T) is classified Uncertain significance in CDC42BPG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-19). AlphaMissense: likely benign (0.1172); Ultra-rare (popmax 0.0686%, mid).

How common is CDC42BPG p.Arg882Cys (c.2644C>T) in the general population?

CDC42BPG p.Arg882Cys (c.2644C>T) is ultra-rare (popmax 0.0686%, mid) (gnomAD).

What do computational predictors say about CDC42BPG p.Arg882Cys (c.2644C>T)?

AlphaMissense predicts likely benign (score 0.1172) — an in-silico prediction, not a clinical call.

CDC42BPG p.Arg882Cys

c.2644C>T · rs71539680 · VCV2364696

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1172 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0686%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1172	likely benign
REVEL	0.465	indeterminate
SaProt	LLR -6.97	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 9.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 17 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	32.0	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 0.0686% Middle Eastern · 4/5,834 alleles

Filtering AF 0.0233% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.014%

Overall 0.00261% 40/1,532,480 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0686%	1,458
Admixed American	0.012%	8,337
Remaining individualsnot grpmax-eligible	0.0118%	8,488
African / African-American	0.011%	9,092
South Asian	0.00728%	13,744
East Asian	0.00246%	40,698
European (non-Finnish)	0.000703%	142,276

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.Arg882Cys
Coding: c.2644C>T
MANE Select: NM_017525
dbSNP: rs71539680
Type: single nucleotide variant
Location: chr11:64833318 (GRCh38)
Gene constraint: LOEUF 1.039 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.90
Residue 882: the 'disordered' region

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-arg882cys (accessed [today's date]).

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