Is CDC25B p.Val162Met (c.484G>A) pathogenic?

CDC25B p.Val162Met (c.484G>A) is classified Uncertain significance in CDC25B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: likely benign (0.1736); Ultra-rare (popmax 0.0527%, sas).

How common is CDC25B p.Val162Met (c.484G>A) in the general population?

CDC25B p.Val162Met (c.484G>A) is ultra-rare (popmax 0.0527%, sas) (gnomAD).

What do computational predictors say about CDC25B p.Val162Met (c.484G>A)?

AlphaMissense predicts likely benign (score 0.1736) — an in-silico prediction, not a clinical call.

CDC25B p.Val162Met

c.484G>A · rs375465916 · VCV3140813

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1736 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0527%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1736	likely benign
REVEL	0.243	benign-leaning
SaProt	LLR -8.12	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 9.9	GERP 1.6, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 4,737 bp · p 0.23 · regional, not allelic
Overall
CADD	25.3	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 0.0527% South Asian · 48/91,086 alleles

Filtering AF 0.0408% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0366%

Overall 0.00515% 83/1,610,702 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0527%	1,898
European (non-Finnish)	0.00288%	34,706
Remaining individualsnot grpmax-eligible	0.0016%	62,460

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: CDC25B
Protein: p.Val162Met
Coding: c.484G>A
MANE Select: NM_021873
dbSNP: rs375465916
Type: single nucleotide variant
Location: chr20:3800767 (GRCh38)
Gene constraint: LOEUF 0.641 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.43 · 19 PDB

Full CDC25B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC25B p.Ala124Val Uncertain significance ★ ⚠ same type
CDC25B p.Ala171Val Uncertain significance ★ ⚠ same type
CDC25B p.Ala231Thr Uncertain significance ★ ⚠ same type
CDC25B p.Ala23Ser Uncertain significance ★ ⚠ same type
CDC25B p.Ala252Asp Uncertain significance ★ ⚠ same type
CDC25B p.Ala463Thr Uncertain significance ★ ⚠ same type
CDC25B p.Ala46Ser Uncertain significance ★ ⚠ same type
CDC25B p.Ala48Ser 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/cdc25b-p-val162met (accessed [today's date]).

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