Is CDC25C p.Thr9Ala (c.25A>G) pathogenic?

CDC25C p.Thr9Ala (c.25A>G) is classified Uncertain significance in CDC25C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-24). AlphaMissense: likely benign (0.0599); Very rare (popmax 0.00133%, afr).

How common is CDC25C p.Thr9Ala (c.25A>G) in the general population?

CDC25C p.Thr9Ala (c.25A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CDC25C p.Thr9Ala (c.25A>G)?

AlphaMissense predicts likely benign (score 0.0599) — an in-silico prediction, not a clinical call.

CDC25C p.Thr9Ala

c.25A>G · rs1257271744 · VCV3140819

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0599 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0599	likely benign
REVEL	0.006	strongly benign-leaning
SaProt	LLR -5.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Regional constraint	o/e 0.90	unconstrained · MANE · 45 kb · p 0.018 · regional, not allelic
Overall
CADD	0.025	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,932 alleles

Overall 0.000657% 1/152,196 alleles · very rare

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: CDC25C
Protein: p.Thr9Ala
Coding: c.25A>G
MANE Select: NM_001790
dbSNP: rs1257271744
Type: single nucleotide variant
Location: chr5:138331156 (GRCh38)
Gene constraint: LOEUF 1.175 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.78 · 6 PDB
Residue 9: the 'disordered' region

Full CDC25C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC25C p.Arg136Cys Uncertain significance ★ ⚠ same type
CDC25C p.Arg208Lys Uncertain significance ★ ⚠ same type
CDC25C p.Arg213Cys Uncertain significance ★ ⚠ same type
CDC25C p.Arg26Met Uncertain significance ★ ⚠ same type
CDC25C p.Arg331Cys Uncertain significance ★ ⚠ same type
CDC25C p.Arg370Gly Uncertain significance ★ ⚠ same type
CDC25C p.Arg383Gly Uncertain significance ★ ⚠ same type
CDC25C p.Arg392His 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/cdc25c-p-thr9ala (accessed [today's date]).

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