Is CDC25A p.Ser88Phe (c.263C>T) pathogenic?

CDC25A p.Ser88Phe (c.263C>T) is classified Likely pathogenic in CDC25A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely benign (0.3164); Ultra-rare (popmax 0.0144%, nfe); Associated with autosomal dominant polycystic liver disease.

What condition is associated with CDC25A p.Ser88Phe (c.263C>T)?

CDC25A p.Ser88Phe (c.263C>T) is associated with autosomal dominant polycystic liver disease (ClinVar).

How common is CDC25A p.Ser88Phe (c.263C>T) in the general population?

CDC25A p.Ser88Phe (c.263C>T) is ultra-rare (popmax 0.0144%, nfe) (gnomAD).

What do computational predictors say about CDC25A p.Ser88Phe (c.263C>T)?

AlphaMissense predicts likely benign (score 0.3164) — an in-silico prediction, not a clinical call.

CDC25A p.Ser88Phe

c.263C>T · rs3731499 · VCV1255549

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3164 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0144%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal dominant polycystic liver disease

Computational evidence

Protein change
AlphaMissense	0.3164	likely benign ⚠ discordant with ClinVar
REVEL	0.247	benign-leaning
SaProt	LLR -9.68	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 9.8	GERP 2.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 22 kb · p 0.0072 · regional, not allelic
Overall
CADD	25.3	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 0.0144% European (non-Finnish) · 168/1,170,384 alleles

Filtering AF 0.0126% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.0115% 183/1,588,730 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0144%	6,967
African / African-American	0.0123%	8,115
Remaining individualsnot grpmax-eligible	0.0065%	15,389
Admixed American	0.00186%	53,762
Finnishnot grpmax-eligible	0.00157%	63,674

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: CDC25A
Protein: p.Ser88Phe
Coding: c.263C>T
MANE Select: NM_001789
dbSNP: rs3731499
Type: single nucleotide variant
Location: chr3:48184680 (GRCh38)
Gene constraint: LOEUF 0.489 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 63.93 · 2 PDB
Residue 88: a modified residue (phosphoserine; by nek11); a UniProt-annotated variant site (in)

Full CDC25A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant polycystic liver disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDC25A p.Asn375Ser Uncertain significance ★ ⚠ same condition
CDC25A p.Thr349Ile Uncertain significance ★ ⚠ same condition
CDC25A p.Lys323Arg Likely benign same condition
CDC25A p.Gln24His Benign ★★ same type
CDC25A p.Ala145Asp Uncertain significance ★ ⚠ same type
CDC25A p.Ala145Gly Uncertain significance ★ ⚠ same type
CDC25A p.Ala22Val Uncertain significance ★ ⚠ same type
CDC25A p.Arg10His 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/cdc25a-p-ser88phe (accessed [today's date]).

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