Is CDC20B p.Glu459Asp (c.1377G>C) pathogenic?

CDC20B p.Glu459Asp (c.1377G>C) is classified Uncertain significance in CDC20B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: ambiguous (0.3429); Absent from gnomAD v4.1.

How common is CDC20B p.Glu459Asp (c.1377G>C) in the general population?

CDC20B p.Glu459Asp (c.1377G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC20B p.Glu459Asp (c.1377G>C)?

AlphaMissense predicts ambiguous (score 0.3429) — an in-silico prediction, not a clinical call.

CDC20B p.Glu459Asp

c.1377G>C · VCV4223189

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3429 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3429	ambiguous
REVEL	0.372	indeterminate
SaProt	LLR -8.37	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.68	GERP -0.62, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 19 kb · p 0.027 · regional, not allelic
Overall
CADD	22.8	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: CDC20B
Protein: p.Glu459Asp
Coding: c.1377G>C
MANE Select: NM_001170402
Type: single nucleotide variant
Location: chr5:55119883 (GRCh38)
Gene constraint: LOEUF 1.25 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.60

Full CDC20B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GPX8 p.Arg117= Benign ★★ same type
CDC20B p.Ala145Ser Uncertain significance ★ ⚠ same type
CDC20B p.Ala64Val Uncertain significance ★ ⚠ same type
CDC20B p.Arg200Gly Uncertain significance ★ ⚠ same type
CDC20B p.Arg353Pro Uncertain significance ★ ⚠ same type
CDC20B p.Arg7Leu Uncertain significance ★ ⚠ same type
CDC20B p.Asn262Asp Uncertain significance ★ ⚠ same type
CDC20B p.Asn262Ser 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/cdc20b-p-glu459asp (accessed [today's date]).

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