WEE2 p.Asp450=
c.1350C>T · rs45535636 · VCV1013566
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.716%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.8 | GERP -7.2 |
| Overall | ||
| CADD | 2.312 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.716%
European (non-Finnish) · 8,452/1,180,024 alleles
Filtering AF
0.703%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.698%
Overall
0.583%
9,409/1,614,158 alleles · rare
exomes 8,845/1,461,854 · genomes 564/152,304 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.716% | 140 |
| Remaining individualsnot grpmax-eligible | 0.542% | 184 |
| Finnishnot grpmax-eligible | 0.384% | 260 |
| Amishnot grpmax-eligible | 0.219% | 456 |
| South Asian | 0.16% | 624 |
| Admixed American | 0.158% | 632 |
| Ashkenazi Jewishnot grpmax-eligible | 0.145% | 688 |
| Middle Eastern | 0.132% | 758 |
| African / African-American | 0.104% | 962 |
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.Asp450=
- Coding
- c.1350C>T
- MANE Select
- NM_001105558
- dbSNP
- rs45535636
- Type
- single nucleotide variant
- Location
- chr7:141725154 (GRCh38)
- Gene constraint
- LOEUF 1.031 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.50 · 1 PDB
- Residue 450
- the protein kinase domain; an α-helix
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-asp450 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown