Is CDC20 p.Arg479Trp (c.1435C>T) pathogenic?

CDC20 p.Arg479Trp (c.1435C>T) is classified Uncertain significance in CDC20 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-15). AlphaMissense: likely benign (0.2759); Very rare (popmax 0.0044%, sas).

How common is CDC20 p.Arg479Trp (c.1435C>T) in the general population?

CDC20 p.Arg479Trp (c.1435C>T) is very rare (popmax 0.0044%, sas) (gnomAD).

What do computational predictors say about CDC20 p.Arg479Trp (c.1435C>T)?

AlphaMissense predicts likely benign (score 0.2759) — an in-silico prediction, not a clinical call.

CDC20 p.Arg479Trp

c.1435C>T · VCV3264934

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2759 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0044%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2759	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -10.82	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 1.1, phastCons 0.78
Regional constraint	o/e 0.92	unconstrained · MANE · 162 bp · p 0.5 · regional, not allelic
Overall
CADD	25.5	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 0.0044% South Asian · 4/90,960 alleles

Filtering AF 0.00247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.00316% 51/1,613,548 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,825
South Asiangrpmax	0.0044%	22,740
Admixed American	0.00334%	29,915
European (non-Finnish)	0.00331%	30,254
African / African-American	0.00267%	37,444
East Asian	0.00223%	44,884

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg479Trp
Coding: c.1435C>T
MANE Select: NM_001255
Type: single nucleotide variant
Location: chr1:43363064 (GRCh38)
Gene constraint: LOEUF 0.744 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.39 · 17 PDB
Residue 479: 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); a UniProt-annotated variant site (in)

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-arg479trp (accessed [today's date]).

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