Is CDC42BPG p.Pro1504Ala (c.4510C>G) pathogenic?

CDC42BPG p.Pro1504Ala (c.4510C>G) is classified Uncertain significance in CDC42BPG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: likely benign (0.0577); Ultra-rare (popmax 0.0847%, sas).

How common is CDC42BPG p.Pro1504Ala (c.4510C>G) in the general population?

CDC42BPG p.Pro1504Ala (c.4510C>G) is ultra-rare (popmax 0.0847%, sas) (gnomAD).

What do computational predictors say about CDC42BPG p.Pro1504Ala (c.4510C>G)?

AlphaMissense predicts likely benign (score 0.0577) — an in-silico prediction, not a clinical call.

CDC42BPG p.Pro1504Ala

c.4510C>G · rs760294420 · VCV2490127

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0577 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0847%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0577	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -6.01	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 -0.11	GERP -0.58, phastCons 0.058
Regional constraint	o/e 1.21	unconstrained · MANE · 3,214 bp · p 0.00049 · regional, not allelic
Overall
CADD	12.91	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 0.0847% South Asian · 72/84,964 alleles

Filtering AF 0.069% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0632%

Overall 0.00503% 79/1,569,622 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0847%	1,180
Middle Eastern	0.0338%	2,955
Remaining individualsnot grpmax-eligible	0.00658%	15,189
European (non-Finnish)	8.64e-05%	1,158,024

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.Pro1504Ala
Coding: c.4510C>G
MANE Select: NM_017525
dbSNP: rs760294420
Type: single nucleotide variant
Location: chr11:64826674 (GRCh38)
Gene constraint: LOEUF 1.039 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.90
Residue 1504: 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-pro1504ala (accessed [today's date]).

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