Is CDC42BPG p.Arg444Gln (c.1331G>A) pathogenic?

CDC42BPG p.Arg444Gln (c.1331G>A) is classified Likely benign in CDC42BPG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely benign (0.0615); Rare (popmax 0.291%, nfe).

How common is CDC42BPG p.Arg444Gln (c.1331G>A) in the general population?

CDC42BPG p.Arg444Gln (c.1331G>A) is rare (popmax 0.291%, nfe) (gnomAD).

What do computational predictors say about CDC42BPG p.Arg444Gln (c.1331G>A)?

AlphaMissense predicts likely benign (score 0.0615) — an in-silico prediction, not a clinical call.

CDC42BPG p.Arg444Gln

c.1331G>A · VCV4650869

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0615 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.291%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0615	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -5.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.1	GERP -1.9
Regional constraint	o/e 0.90	unconstrained · MANE · 17 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	9.249	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 0.291% European (non-Finnish) · 3,417/1,174,520 alleles

Filtering AF 0.283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.279%

Overall 0.23% 3,692/1,602,382 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.291%	344
Remaining individualsnot grpmax-eligible	0.183%	548
Finnishnot grpmax-eligible	0.0865%	1,156
African / African-American	0.0524%	1,910
Admixed American	0.0509%	1,965
South Asian	0.0401%	2,497
Middle Eastern	0.0173%	5,792
Ashkenazi Jewishnot grpmax-eligible	0.00344%	29,084
East Asian	0.00225%	44,428

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.Arg444Gln
Coding: c.1331G>A
MANE Select: NM_017525
Type: single nucleotide variant
Location: chr11:64836792 (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.Arg444Trp 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-arg444gln (accessed [today's date]).

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