Is WEE2 p.Ala300Val (c.899C>T) pathogenic?

WEE2 p.Ala300Val (c.899C>T) is classified Uncertain significance in WEE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-17). AlphaMissense: likely benign (0.0883); Ultra-rare (popmax 0.01%, amr).

How common is WEE2 p.Ala300Val (c.899C>T) in the general population?

WEE2 p.Ala300Val (c.899C>T) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about WEE2 p.Ala300Val (c.899C>T)?

AlphaMissense predicts likely benign (score 0.0883) — an in-silico prediction, not a clinical call.

WEE2 p.Ala300Val

c.899C>T · rs368459117 · VCV3190459

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0883 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0883	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -7.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.81	GERP 3.5, phastCons 0.24
Regional constraint	o/e 0.92	unconstrained · MANE · 22 kb · p 0.042 · regional, not allelic
Overall
CADD	13.68	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 0.01% Admixed American · 6/60,000 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00387%

Overall 0.00458% 74/1,614,002 alleles · ultra-rare exomes 64/1,461,828 · genomes 10/152,174 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,000
European (non-Finnish)	0.00534%	18,730
Remaining individualsnot grpmax-eligible	0.0048%	20,829
African / African-American	0.00267%	37,456

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: WEE2
Protein: p.Ala300Val
Coding: c.899C>T
MANE Select: NM_001105558
dbSNP: rs368459117
Type: single nucleotide variant
Location: chr7:141723152 (GRCh38)
Gene constraint: LOEUF 1.031 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.50 · 1 PDB
Residue 300: 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.Ala384Thr Uncertain significance ★ ⚠ same type
WEE2 p.Ala427Thr 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-ala300val (accessed [today's date]).

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