Is CDC25B p.Ala231Thr (c.691G>A) pathogenic?

CDC25B p.Ala231Thr (c.691G>A) is classified Uncertain significance in CDC25B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: ambiguous (0.4211); Absent from gnomAD v4.1.

How common is CDC25B p.Ala231Thr (c.691G>A) in the general population?

CDC25B p.Ala231Thr (c.691G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC25B p.Ala231Thr (c.691G>A)?

AlphaMissense predicts ambiguous (score 0.4211) — an in-silico prediction, not a clinical call.

CDC25B p.Ala231Thr

c.691G>A · VCV4223222

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4211 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4211	ambiguous
REVEL	0.232	benign-leaning
SaProt	LLR -6.19	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 4,737 bp · p 0.23 · regional, not allelic
Overall
CADD	24.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDC25B
Protein: p.Ala231Thr
Coding: c.691G>A
MANE Select: NM_021873
Type: single nucleotide variant
Location: chr20:3801079 (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.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
CDC25B p.Ala549Asp 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-ala231thr (accessed [today's date]).

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