Is CDC20 p.Ile229Met (c.687A>G) pathogenic?

CDC20 p.Ile229Met (c.687A>G) is classified Uncertain significance in CDC20 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-28). AlphaMissense: likely pathogenic (0.6776); Absent from gnomAD v4.1.

How common is CDC20 p.Ile229Met (c.687A>G) in the general population?

CDC20 p.Ile229Met (c.687A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC20 p.Ile229Met (c.687A>G)?

AlphaMissense predicts likely pathogenic (score 0.6776) — an in-silico prediction, not a clinical call.

CDC20 p.Ile229Met

c.687A>G · VCV3998456

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6776 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6776	likely pathogenic
REVEL	0.218	benign-leaning
SaProt	LLR -12.00	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.096	GERP -3.6, phastCons 0.007
Regional constraint	o/e 0.78	unconstrained · MANE · 1,422 bp · p 7.3e-05 · regional, not allelic
Overall
CADD	14.65	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: CDC20
Protein: p.Ile229Met
Coding: c.687A>G
MANE Select: NM_001255
Type: single nucleotide variant
Location: chr1:43360323 (GRCh38)
Gene constraint: LOEUF 0.744 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.39 · 17 PDB
Residue 229: 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 β-strand

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

Similar variants

CDC20 p.Ile229Val Likely benign ★ same residue
CDC20 p.Glu484= Benign ★★ same type
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

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-ile229met (accessed [today's date]).

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