Is CDC42BPA p.Pro341Ser (c.1021C>T) pathogenic?

CDC42BPA p.Pro341Ser (c.1021C>T) is classified Uncertain significance in CDC42BPA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-19). AlphaMissense: likely benign (0.0952); Ultra-rare (popmax 0.022%, sas).

How common is CDC42BPA p.Pro341Ser (c.1021C>T) in the general population?

CDC42BPA p.Pro341Ser (c.1021C>T) is ultra-rare (popmax 0.022%, sas) (gnomAD).

What do computational predictors say about CDC42BPA p.Pro341Ser (c.1021C>T)?

AlphaMissense predicts likely benign (score 0.0952) — an in-silico prediction, not a clinical call.

CDC42BPA p.Pro341Ser

c.1021C>T · VCV3829775

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0952 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.022%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0952	likely benign
REVEL	0.401	indeterminate
SaProt	LLR -9.53	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 8.6	GERP 2.8, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 174 kb · p 3.3e-14 · regional, not allelic
Overall
CADD	26.8	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 0.022% South Asian · 20/91,058 alleles

Filtering AF 0.0145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00137% 20/1,461,558 alleles · ultra-rare

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: CDC42BPA
Protein: p.Pro341Ser
Coding: c.1021C>T
MANE Select: NM_001394014
Type: single nucleotide variant
Location: chr1:227145611 (GRCh38)
Gene constraint: LOEUF 0.464 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.69
Residue 341: the protein kinase domain

Full CDC42BPA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC42BPA p.Pro341Leu Uncertain significance ★ ⚠ same residue
CDC42BPA p.Arg1681Gln Uncertain significance ★★ ⚠ same type
CDC42BPA p.Ser1661= Benign ★★ same type
CDC42BPA p.Ser884= Benign/Likely benign ★★ same type
CDC42BPA p.Thr290= Benign ★★ same type
CDC42BPA p.Ala1106Pro Uncertain significance ★ ⚠ same type
CDC42BPA p.Ala1170Val Uncertain significance ★ ⚠ same type
CDC42BPA p.Ala1256Thr 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/cdc42bpa-p-pro341ser (accessed [today's date]).

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