Is WEE2 p.Pro413Ala (c.1237C>G) pathogenic?

WEE2 p.Pro413Ala (c.1237C>G) is classified Uncertain significance in WEE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: likely benign (0.1465); Absent from gnomAD v4.1.

How common is WEE2 p.Pro413Ala (c.1237C>G) in the general population?

WEE2 p.Pro413Ala (c.1237C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about WEE2 p.Pro413Ala (c.1237C>G)?

AlphaMissense predicts likely benign (score 0.1465) — an in-silico prediction, not a clinical call.

WEE2 p.Pro413Ala

c.1237C>G · rs1431611762 · VCV2492347

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1465 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1465	likely benign
REVEL	0.311	indeterminate
SaProt	LLR -7.92	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.3	GERP 5.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 22 kb · p 0.042 · regional, not allelic
Overall
CADD	23.0	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: WEE2
Protein: p.Pro413Ala
Coding: c.1237C>G
MANE Select: NM_001105558
dbSNP: rs1431611762
Type: single nucleotide variant
Location: chr7:141725041 (GRCh38)
Gene constraint: LOEUF 1.031 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.50 · 1 PDB
Residue 413: the protein kinase domain; an α-helix

Full WEE2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

WEE2 p.Gly357Arg Uncertain significance ★★ ⚠ same type
WEE2 p.Ile417Thr Uncertain significance ★★ same type
WEE2 p.Tyr526Asp Benign/Likely benign ★★ same type
WEE2 p.Gln288Ter Pathogenic ★ same type
WEE2 c.585+3A>G Uncertain significance ★ same type
WEE2 p.Ala194Asp Uncertain significance ★ ⚠ same type
WEE2 p.Ala300Val Uncertain significance ★ ⚠ same type
WEE2 p.Ala384Thr 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/wee2-p-pro413ala (accessed [today's date]).

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