Is CDC40 p.Glu211Asp (c.633A>C) pathogenic?

CDC40 p.Glu211Asp (c.633A>C) is classified Uncertain significance in CDC40 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.0994); Absent from gnomAD v4.1.

How common is CDC40 p.Glu211Asp (c.633A>C) in the general population?

CDC40 p.Glu211Asp (c.633A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC40 p.Glu211Asp (c.633A>C)?

AlphaMissense predicts likely benign (score 0.0994) — an in-silico prediction, not a clinical call.

CDC40 p.Glu211Asp

c.633A>C · VCV4223266

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0994 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0994	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -8.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.32	acceptor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 5.3	GERP 1.9, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 39 kb · p 5.5e-07 · regional, not allelic
Overall
CADD	19.6	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: CDC40
Protein: p.Glu211Asp
Coding: c.633A>C
MANE Select: NM_015891
Type: single nucleotide variant
Location: chr6:110210709 (GRCh38)
Gene constraint: LOEUF 0.491 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 86.76 · 30 PDB
Residue 211: an α-helix; the 'disordered' region

Full CDC40 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC40 p.Ala33Gly Uncertain significance ★ ⚠ same type
CDC40 p.Ala466Thr Uncertain significance ★ ⚠ same type
CDC40 p.Arg129Lys Uncertain significance ★ ⚠ same type
CDC40 p.Arg322Trp Uncertain significance ★ ⚠ same type
CDC40 p.Arg323Cys Uncertain significance ★ ⚠ same type
CDC40 p.Asn382His Uncertain significance ★ ⚠ same type
CDC40 p.Asn430Lys Uncertain significance ★ ⚠ same type
CDC40 p.Asn497Thr 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/cdc40-p-glu211asp (accessed [today's date]).

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