Is CDC42BPB p.Asp49Val (c.146A>T) pathogenic?

CDC42BPB p.Asp49Val (c.146A>T) is classified Uncertain significance in CDC42BPB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-02). AlphaMissense: likely pathogenic (0.9591); Absent from gnomAD v4.1.

How common is CDC42BPB p.Asp49Val (c.146A>T) in the general population?

CDC42BPB p.Asp49Val (c.146A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC42BPB p.Asp49Val (c.146A>T)?

AlphaMissense predicts likely pathogenic (score 0.9591) — an in-silico prediction, not a clinical call.

CDC42BPB p.Asp49Val

c.146A>T · VCV3393567

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9591 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9591	likely pathogenic
REVEL	0.181	moderately benign-leaning
SaProt	LLR -9.91	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 1.7, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 45 kb · p 0.73 · regional, not allelic
Overall
CADD	24.4	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

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: CDC42BPB
Protein: p.Asp49Val
Coding: c.146A>T
MANE Select: NM_006035
Type: single nucleotide variant
Location: chr14:103057028 (GRCh38)
Gene constraint: LOEUF 0.235 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 76.28 · 6 PDB

Full CDC42BPB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC42BPB c.2726+1G>A Pathogenic/Likely pathogenic ★★ same type
CDC42BPB p.Ala177Val Likely pathogenic ★★ same type
CDC42BPB p.Arg122Ter Pathogenic/Likely pathogenic ★★ same type
CDC42BPB p.Arg867Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
CDC42BPB p.Arg876Pro Likely pathogenic ★★ ⚠ same type
CDC42BPB p.Asp175Tyr Likely pathogenic ★★ same type
CDC42BPB p.Ser1530Ter Likely pathogenic ★★ same type
CDC42BPB p.Arg509Ter 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/cdc42bpb-p-asp49val (accessed [today's date]).

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