Is CDC20 p.Phe473Leu (c.1417T>C) pathogenic?

CDC20 p.Phe473Leu (c.1417T>C) is classified Uncertain significance in CDC20 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-20). AlphaMissense: likely pathogenic (0.996); Ultra-rare (popmax 0.0231%, sas).

How common is CDC20 p.Phe473Leu (c.1417T>C) in the general population?

CDC20 p.Phe473Leu (c.1417T>C) is ultra-rare (popmax 0.0231%, sas) (gnomAD).

What do computational predictors say about CDC20 p.Phe473Leu (c.1417T>C)?

AlphaMissense predicts likely pathogenic (score 0.996) — an in-silico prediction, not a clinical call.

CDC20 p.Phe473Leu

c.1417T>C · VCV3264932

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.996 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.996	likely pathogenic · top 8% in CDC20
REVEL	0.554	indeterminate
SaProt	LLR -9.17	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 162 bp · p 0.5 · regional, not allelic
Overall
CADD	30.0	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

Grpmax group 0.0231% South Asian · 21/90,968 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.00149% 24/1,613,660 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0231%	4,332
Remaining individualsnot grpmax-eligible	0.0016%	62,496
African / African-American	0.00133%	74,950
European (non-Finnish)	8.48e-05%	1,179,889

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.Phe473Leu
Coding: c.1417T>C
MANE Select: NM_001255
Type: single nucleotide variant
Location: chr1:43363046 (GRCh38)
Gene constraint: LOEUF 0.744 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.39 · 17 PDB
Residue 473: 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.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
CDC20 p.Arg162Gly 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-phe473leu (accessed [today's date]).

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