Is WEE2 p.Val451Ile (c.1351G>A) pathogenic?

WEE2 p.Val451Ile (c.1351G>A) is classified Likely benign in WEE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: likely benign (0.0603); Ultra-rare (popmax 0.0245%, eas).

How common is WEE2 p.Val451Ile (c.1351G>A) in the general population?

WEE2 p.Val451Ile (c.1351G>A) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

What do computational predictors say about WEE2 p.Val451Ile (c.1351G>A)?

AlphaMissense predicts likely benign (score 0.0603) — an in-silico prediction, not a clinical call.

WEE2 p.Val451Ile

c.1351G>A · rs956821646 · VCV2254000

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0603 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0603	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -4.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.85	GERP -5.4
Regional constraint	o/e 0.92	unconstrained · MANE · 22 kb · p 0.042 · regional, not allelic
Overall
CADD	0.037	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0245% East Asian · 11/44,898 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00328% 53/1,614,052 alleles · ultra-rare exomes 50/1,461,870 · genomes 3/152,182 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0512%	1,953
East Asiangrpmax	0.0245%	4,082
Admixed American	0.00333%	30,002
African / African-American	0.00267%	37,464
European (non-Finnish)	0.000508%	196,669

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val451Ile
Coding: c.1351G>A
MANE Select: NM_001105558
dbSNP: rs956821646
Type: single nucleotide variant
Location: chr7:141725155 (GRCh38)
Gene constraint: LOEUF 1.031 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.50 · 1 PDB
Residue 451: the protein kinase domain

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-val451ile (accessed [today's date]).

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