Is CDC25B p.Arg330Trp (c.988C>T) pathogenic?

CDC25B p.Arg330Trp (c.988C>T) is classified Uncertain significance in CDC25B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: ambiguous (0.514); Very rare (popmax 0.00577%, nfe).

How common is CDC25B p.Arg330Trp (c.988C>T) in the general population?

CDC25B p.Arg330Trp (c.988C>T) is very rare (popmax 0.00577%, nfe) (gnomAD).

What do computational predictors say about CDC25B p.Arg330Trp (c.988C>T)?

AlphaMissense predicts ambiguous (score 0.514) — an in-silico prediction, not a clinical call.

CDC25B p.Arg330Trp

c.988C>T · rs376224294 · VCV2391097

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.514 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00577%, nfe)

Computational evidence

Protein change
AlphaMissense	0.514	ambiguous
REVEL	0.368	indeterminate
SaProt	LLR -11.69	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 3,688 bp · p 1.2e-06 · regional, not allelic
Overall
CADD	32.0	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 0.00577% European (non-Finnish) · 68/1,178,006 alleles

Filtering AF 0.00462% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00423%

Overall 0.00454% 73/1,609,136 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00577%	17,324
East Asian	0.00449%	22,268
African / African-American	0.00268%	37,354
South Asian	0.00111%	90,070

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: CDC25B
Protein: p.Arg330Trp
Coding: c.988C>T
MANE Select: NM_021873
dbSNP: rs376224294
Type: single nucleotide variant
Location: chr20:3801990 (GRCh38)
Gene constraint: LOEUF 0.641 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.43 · 19 PDB

Full CDC25B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC25B p.Ala124Val Uncertain significance ★ ⚠ same type
CDC25B p.Ala171Val Uncertain significance ★ ⚠ same type
CDC25B p.Ala231Thr Uncertain significance ★ ⚠ same type
CDC25B p.Ala23Ser Uncertain significance ★ ⚠ same type
CDC25B p.Ala252Asp Uncertain significance ★ ⚠ same type
CDC25B p.Ala463Thr Uncertain significance ★ ⚠ same type
CDC25B p.Ala46Ser Uncertain significance ★ ⚠ same type
CDC25B p.Ala48Ser 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/cdc25b-p-arg330trp (accessed [today's date]).

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