Is CDC25C p.Asp418Tyr (c.1252G>T) pathogenic?

CDC25C p.Asp418Tyr (c.1252G>T) is classified Uncertain significance in CDC25C (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.2278); Absent from gnomAD v4.1.

How common is CDC25C p.Asp418Tyr (c.1252G>T) in the general population?

CDC25C p.Asp418Tyr (c.1252G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC25C p.Asp418Tyr (c.1252G>T)?

AlphaMissense predicts likely benign (score 0.2278) — an in-silico prediction, not a clinical call.

CDC25C p.Asp418Tyr

c.1252G>T · VCV3488341

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2278 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2278	likely benign
REVEL	0.306	indeterminate
SaProt	LLR -9.95	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -1.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 45 kb · p 0.018 · regional, not allelic
Overall
CADD	24.1	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

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: CDC25C
Protein: p.Asp418Tyr
Coding: c.1252G>T
MANE Select: NM_001790
Type: single nucleotide variant
Location: chr5:138286042 (GRCh38)
Gene constraint: LOEUF 1.175 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.78 · 6 PDB
Residue 418: the rhodanese domain; an α-helix

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-asp418tyr (accessed [today's date]).

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