Is CDC20B p.Arg353His (c.1058G>A) pathogenic?

CDC20B p.Arg353His (c.1058G>A) is classified Likely benign in CDC20B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely benign (0.0589); Ultra-rare (popmax 0.0267%, eas).

How common is CDC20B p.Arg353His (c.1058G>A) in the general population?

CDC20B p.Arg353His (c.1058G>A) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

What do computational predictors say about CDC20B p.Arg353His (c.1058G>A)?

AlphaMissense predicts likely benign (score 0.0589) — an in-silico prediction, not a clinical call.

CDC20B p.Arg353His

c.1058G>A · rs140191094 · VCV3140787

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0589 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0589	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -6.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.2	GERP -3.4
Regional constraint	o/e 0.89	unconstrained · MANE · 19 kb · p 0.027 · regional, not allelic
Overall
CADD	0.954	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 0.0267% East Asian · 12/44,884 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00322% 52/1,614,112 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0267%	3,740
Admixed American	0.0217%	4,617
Remaining individualsnot grpmax-eligible	0.0032%	31,251
African / African-American	0.00267%	37,504
European (non-Finnish)	0.00186%	53,637
South Asian	0.0011%	91,080

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.Arg353His
Coding: c.1058G>A
MANE Select: NM_001170402
dbSNP: rs140191094
Type: single nucleotide variant
Location: chr5:55124960 (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

CDC20B p.Arg353Pro Uncertain significance ★ ⚠ same residue
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.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-arg353his (accessed [today's date]).

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