Is CDC20B p.Leu497Phe (c.1491G>T) pathogenic?

CDC20B p.Leu497Phe (c.1491G>T) is classified Uncertain significance in CDC20B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely benign (0.1622); Ultra-rare (popmax 0.0495%, mid).

How common is CDC20B p.Leu497Phe (c.1491G>T) in the general population?

CDC20B p.Leu497Phe (c.1491G>T) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

What do computational predictors say about CDC20B p.Leu497Phe (c.1491G>T)?

AlphaMissense predicts likely benign (score 0.1622) — an in-silico prediction, not a clinical call.

CDC20B p.Leu497Phe

c.1491G>T · VCV4223182

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1622 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1622	likely benign
REVEL	0.294	indeterminate
SaProt	LLR -11.13	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP 1.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 19 kb · p 0.027 · regional, not allelic
Overall
CADD	23.0	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 0.0495% Middle Eastern · 3/6,058 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00718%

Overall 0.00198% 29/1,461,702 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,019
Remaining individualsnot grpmax-eligible	0.0096%	10,417
European (non-Finnish)	0.00161%	62,101
South Asian	0.0011%	91,068

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: CDC20B
Protein: p.Leu497Phe
Coding: c.1491G>T
MANE Select: NM_001170402
Type: single nucleotide variant
Location: chr5:55114287 (GRCh38)
Gene constraint: LOEUF 1.25 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.60

Full CDC20B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GPX8 p.Arg117= Benign ★★ same type
CDC20B p.Ala145Ser Uncertain significance ★ ⚠ same type
CDC20B p.Ala64Val Uncertain significance ★ ⚠ same type
CDC20B p.Arg200Gly Uncertain significance ★ ⚠ same type
CDC20B p.Arg353Pro Uncertain significance ★ ⚠ same type
CDC20B p.Arg7Leu Uncertain significance ★ ⚠ same type
CDC20B p.Asn262Asp Uncertain significance ★ ⚠ same type
CDC20B p.Asn262Ser 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/cdc20b-p-leu497phe (accessed [today's date]).

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