Is CDC25C p.Ile62Ser (c.185T>G) pathogenic?

CDC25C p.Ile62Ser (c.185T>G) is classified Uncertain significance in CDC25C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely benign (0.1181); Very rare (popmax 0.00667%, amr).

How common is CDC25C p.Ile62Ser (c.185T>G) in the general population?

CDC25C p.Ile62Ser (c.185T>G) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about CDC25C p.Ile62Ser (c.185T>G)?

AlphaMissense predicts likely benign (score 0.1181) — an in-silico prediction, not a clinical call.

CDC25C p.Ile62Ser

c.185T>G · VCV4650826

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1181 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1181	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -4.71	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 5.1	GERP 1.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 45 kb · p 0.018 · regional, not allelic
Overall
CADD	16.69	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 0.00667% Admixed American · 4/60,000 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000344% 5/1,455,004 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,000
Remaining individualsnot grpmax-eligible	0.00161%	62,216

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.Ile62Ser
Coding: c.185T>G
MANE Select: NM_001790
Type: single nucleotide variant
Location: chr5:138330996 (GRCh38)
Gene constraint: LOEUF 1.175 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.78 · 6 PDB

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-ile62ser (accessed [today's date]).

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