Is CDC42BPG p.Val969Met (c.2905G>A) pathogenic?

CDC42BPG p.Val969Met (c.2905G>A) is classified Uncertain significance in CDC42BPG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-02). AlphaMissense: ambiguous (0.3638); Ultra-rare (popmax 0.0133%, nfe).

How common is CDC42BPG p.Val969Met (c.2905G>A) in the general population?

CDC42BPG p.Val969Met (c.2905G>A) is ultra-rare (popmax 0.0133%, nfe) (gnomAD).

What do computational predictors say about CDC42BPG p.Val969Met (c.2905G>A)?

AlphaMissense predicts ambiguous (score 0.3638) — an in-silico prediction, not a clinical call.

CDC42BPG p.Val969Met

c.2905G>A · rs199543708 · VCV2401024

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3638 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3638	ambiguous
REVEL	0.388	indeterminate
SaProt	LLR -10.77	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 17 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	25.6	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 0.0133% European (non-Finnish) · 157/1,179,142 alleles

Filtering AF 0.0116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.0106% 171/1,612,044 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0133%	7,510
Remaining individualsnot grpmax-eligible	0.00962%	10,395
Admixed American	0.00501%	19,965
South Asian	0.0044%	22,726
Finnishnot grpmax-eligible	0.00158%	63,416

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.Val969Met
Coding: c.2905G>A
MANE Select: NM_017525
dbSNP: rs199543708
Type: single nucleotide variant
Location: chr11:64832704 (GRCh38)
Gene constraint: LOEUF 1.039 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.90
Residue 969: 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-val969met (accessed [today's date]).

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