Is CDC42BPG p.Cys421Ser (c.1262G>C) pathogenic?

CDC42BPG p.Cys421Ser (c.1262G>C) is classified Uncertain significance in CDC42BPG (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-22). AlphaMissense: likely benign (0.0954); Absent from gnomAD v4.1.

How common is CDC42BPG p.Cys421Ser (c.1262G>C) in the general population?

CDC42BPG p.Cys421Ser (c.1262G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC42BPG p.Cys421Ser (c.1262G>C)?

AlphaMissense predicts likely benign (score 0.0954) — an in-silico prediction, not a clinical call.

CDC42BPG p.Cys421Ser

c.1262G>C · rs761785900 · VCV2487710

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0954 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0954	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -4.03	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 -2.4	GERP -2.4
Regional constraint	o/e 0.90	unconstrained · MANE · 17 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	4.681	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDC42BPG
Protein: p.Cys421Ser
Coding: c.1262G>C
MANE Select: NM_017525
dbSNP: rs761785900
Type: single nucleotide variant
Location: chr11:64836963 (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.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-cys421ser (accessed [today's date]).

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