Is WEE2 p.Arg200Ter (c.598C>T) pathogenic?

WEE2 p.Arg200Ter (c.598C>T) is classified Pathogenic in WEE2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-04-10). Very rare (popmax 0.00989%, sas); Associated with oocyte maturation defect 5.

What condition is associated with WEE2 p.Arg200Ter (c.598C>T)?

WEE2 p.Arg200Ter (c.598C>T) is associated with oocyte maturation defect 5 (ClinVar).

How common is WEE2 p.Arg200Ter (c.598C>T) in the general population?

WEE2 p.Arg200Ter (c.598C>T) is very rare (popmax 0.00989%, sas) (gnomAD).

WEE2 p.Arg200Ter

c.598C>T · rs754062320 · VCV977297

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00989%, sas)

Conditions

oocyte maturation defect 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 12
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.83	GERP 0.29, phastCons 0.048
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00989% South Asian · 9/91,004 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00376%

Overall 0.0013% 21/1,613,392 alleles · very rare exomes 19/1,461,348 · genomes 2/152,044 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00989%	10,112
East Asian	0.00223%	44,866
Admixed American	0.00167%	59,880
European (non-Finnish)	0.000848%	117,985

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.Arg200Ter
Coding: c.598C>T
MANE Select: NM_001105558
dbSNP: rs754062320
Type: single nucleotide variant
Location: chr7:141719084 (GRCh38)
Gene constraint: LOEUF 1.031 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.50 · 1 PDB

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

Disease context

oocyte maturation defect 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

WEE2 p.Arg200Gln Uncertain significance ★ ⚠ same residue
WEE2 p.Tyr163His Uncertain significance ★ ⚠ same condition
WEE2 p.Arg410Trp Pathogenic ⚠ same condition
WEE2 p.Asp234His Pathogenic same condition
WEE2 p.Glu407= Pathogenic same condition
WEE2 p.Glu75fs Pathogenic/Likely pathogenic ★★ same condition
WEE2 p.His337fs Pathogenic ★ same condition
WEE2 p.Thr493fs Pathogenic same condition

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-arg200ter (accessed [today's date]).

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