Is CDC25A p.Lys323Arg (c.968A>G) pathogenic?

CDC25A p.Lys323Arg (c.968A>G) is classified Likely benign in CDC25A (ClinVar, No assertion criteria, 2 submitters; last evaluated 2021-09-01). AlphaMissense: likely benign (0.0708); Low-frequency (popmax 1.04%, sas); Associated with autosomal dominant polycystic liver disease.

What condition is associated with CDC25A p.Lys323Arg (c.968A>G)?

CDC25A p.Lys323Arg (c.968A>G) is associated with autosomal dominant polycystic liver disease (ClinVar).

How common is CDC25A p.Lys323Arg (c.968A>G) in the general population?

CDC25A p.Lys323Arg (c.968A>G) is low-frequency (popmax 1.04%, sas) (gnomAD).

What do computational predictors say about CDC25A p.Lys323Arg (c.968A>G)?

AlphaMissense predicts likely benign (score 0.0708) — an in-silico prediction, not a clinical call.

CDC25A p.Lys323Arg

c.968A>G · rs202026442 · VCV1255565

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0708 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.04%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal dominant polycystic liver disease

Computational evidence

Protein change
AlphaMissense	0.0708	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -6.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.71 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.8	GERP -0.32, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 22 kb · p 0.0072 · regional, not allelic
Overall
CADD	16.8	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 1.04% South Asian · 943/90,980 alleles

Filtering AF 0.982% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.96%

Overall 0.0794% 1,278/1,610,528 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.04%	96
Ashkenazi Jewishnot grpmax-eligible	0.23%	435
Middle Eastern	0.182%	551
Remaining individualsnot grpmax-eligible	0.103%	975
European (non-Finnish)	0.0155%	6,431
African / African-American	0.00668%	14,980
Admixed American	0.005%	19,987
East Asian	0.00223%	44,838

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.Lys323Arg
Coding: c.968A>G
MANE Select: NM_001789
dbSNP: rs202026442
Type: single nucleotide variant
Location: chr3:48167907 (GRCh38)
Gene constraint: LOEUF 0.489 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 63.93 · 2 PDB

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.Ser88Phe Likely pathogenic ⚠ 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-lys323arg (accessed [today's date]).

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