Is CDC20 p.Glu484= (c.1452G>A) pathogenic?

CDC20 p.Glu484= (c.1452G>A) is classified Benign in CDC20 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Common (popmax 5.18%, amr) — too common for a highly-penetrant pathogenic allele.

CDC20 p.Glu484=

Q: How common is CDC20 p.Glu484= (c.1452G>A) in the general population?

CDC20 p.Glu484= (c.1452G>A) is common (popmax 5.18%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1452G>A · rs2069388 · VCV778231

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.18%, amr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -4.3, phastCons 1
Overall
CADD	6.042	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.18% Admixed American · 3,103/59,868 alleles

Filtering AF 5.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.97%

Overall 0.199% 3,214/1,613,560 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	5.18%	19
Remaining individualsnot grpmax-eligible	0.123%	812
African / African-American	0.0294%	3,404
European (non-Finnish)	0.00102%	98,322

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: CDC20
Protein: p.Glu484=
Coding: c.1452G>A
MANE Select: NM_001255
dbSNP: rs2069388
Type: single nucleotide variant
Location: chr1:43363081 (GRCh38)
Gene constraint: LOEUF 0.744 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.39 · 17 PDB
Residue 484: a UniProt-annotated variant site (in ozema14; severely decreased function in metaphase/anaphase transition of meiosis i; does not fully rescue metaphase i arrest in cdc20-knocked down mouse oocytes; decreased function in positive regulation of anaphase-promoting complex-dependent catabolic process; fails to localize to the kinetochore); a UniProt-annotated variant site (in ozema14)

Full CDC20 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC20 p.Val361Ile Benign/Likely benign ★★ same type
CDC20 p.Cys364Ter Likely pathogenic ★ same type
CDC20 c.556+1G>T Conflicting classifications of pathogenicity ★ same type
CDC20 p.Ala140Val Uncertain significance ★ ⚠ same type
CDC20 p.Ala242Val Uncertain significance ★ ⚠ same type
CDC20 p.Ala461Thr Uncertain significance ★ ⚠ same type
CDC20 p.Arg162Gly Uncertain significance ★ ⚠ same type
CDC20 p.Arg260Gln 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/cdc20-p-glu484 (accessed [today's date]).

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