Is WEE2 p.Arg487Trp (c.1459C>T) pathogenic?

WEE2 p.Arg487Trp (c.1459C>T) is classified Uncertain significance in WEE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-01). AlphaMissense: likely benign (0.116); Ultra-rare (popmax 0.0164%, mid).

How common is WEE2 p.Arg487Trp (c.1459C>T) in the general population?

WEE2 p.Arg487Trp (c.1459C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about WEE2 p.Arg487Trp (c.1459C>T)?

AlphaMissense predicts likely benign (score 0.116) — an in-silico prediction, not a clinical call.

WEE2 p.Arg487Trp

c.1459C>T · rs199682855 · VCV1335693

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.116 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.116	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -8.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.42	GERP -1.5
Regional constraint	o/e 0.92	unconstrained · MANE · 22 kb · p 0.042 · regional, not allelic
Overall
CADD	13.45	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 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00375%

Overall 0.00452% 73/1,614,014 alleles · ultra-rare exomes 65/1,461,884 · genomes 8/152,130 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
South Asian	0.00988%	10,120
European (non-Finnish)	0.00492%	20,345
Remaining individualsnot grpmax-eligible	0.0032%	31,243
African / African-American	0.00267%	37,445
East Asian	0.00223%	44,902

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.Arg487Trp
Coding: c.1459C>T
MANE Select: NM_001105558
dbSNP: rs199682855
Type: single nucleotide variant
Location: chr7:141727370 (GRCh38)

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

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-arg487trp (accessed [today's date]).

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