Is CDC20 p.Ala242Val (c.725C>T) pathogenic?

CDC20 p.Ala242Val (c.725C>T) is classified Uncertain significance in CDC20 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-05). AlphaMissense: likely pathogenic (0.9669); Very rare (popmax 0.000508%, nfe).

How common is CDC20 p.Ala242Val (c.725C>T) in the general population?

CDC20 p.Ala242Val (c.725C>T) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about CDC20 p.Ala242Val (c.725C>T)?

AlphaMissense predicts likely pathogenic (score 0.9669) — an in-silico prediction, not a clinical call.

CDC20 p.Ala242Val

c.725C>T · rs2545699030 · VCV2543992

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9669 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9669	likely pathogenic
REVEL	0.503	indeterminate
SaProt	LLR -13.46	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 1,422 bp · p 7.3e-05 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.000508% European (non-Finnish) · 6/1,180,016 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.00041% 6/1,461,862 alleles · very rare

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.Ala242Val
Coding: c.725C>T
MANE Select: NM_001255
dbSNP: rs2545699030
Type: single nucleotide variant
Location: chr1:43360361 (GRCh38)
Gene constraint: LOEUF 0.744 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.39 · 17 PDB
Residue 242: 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.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.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-ala242val (accessed [today's date]).

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