Is WEE2 p.Ala264= (c.792A>G) pathogenic?

WEE2 p.Ala264= (c.792A>G) is classified Benign in WEE2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-18). Common (popmax 75%, afr) — too common for a highly-penetrant pathogenic allele; Associated with WEE2-related disorder.

What condition is associated with WEE2 p.Ala264= (c.792A>G)?

WEE2 p.Ala264= (c.792A>G) is associated with WEE2-related disorder (ClinVar).

WEE2 p.Ala264=

Q: How common is WEE2 p.Ala264= (c.792A>G) in the general population?

WEE2 p.Ala264= (c.792A>G) is common (popmax 75%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.792A>G · rs6967301 · VCV3059633

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 75%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

WEE2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.4	GERP -9.5
Overall
CADD	0.191	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 75% African / African-American · 56,258/74,968 alleles

Filtering AF 74.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 74.3%

Overall 52% 839,272/1,613,268 alleles · common exomes 752,405/1,461,124 · genomes 86,867/152,144 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	75%	1
South Asian	60.3%	2
Amishnot grpmax-eligible	59.5%	2
Middle Eastern	57.2%	2
Ashkenazi Jewishnot grpmax-eligible	56.6%	2
Finnishnot grpmax-eligible	53.2%	2
Remaining individualsnot grpmax-eligible	51.8%	2
Admixed American	50.6%	2
European (non-Finnish)	50.5%	2
East Asian	32.4%	3

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.Ala264=
Coding: c.792A>G
MANE Select: NM_001105558
dbSNP: rs6967301
Type: single nucleotide variant
Location: chr7:141720968 (GRCh38)
Gene constraint: LOEUF 1.031 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.50 · 1 PDB
Residue 264: the protein kinase domain; an α-helix

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

Disease context

WEE2-related disorder

Similar variants

WEE2 c.1536-9G>A Likely benign same condition
WEE2 p.Asn62= Likely benign same condition
WEE2 p.Lys134= Likely benign same condition
WEE2 p.Ser100= Likely benign same condition
WEE2 p.Glu75fs Pathogenic/Likely pathogenic ★★ same condition
WEE2 p.Gly357Arg Uncertain significance ★★ ⚠ same type
WEE2 p.Ile417Thr Uncertain significance ★★ same type
WEE2 p.Tyr526Asp Benign/Likely benign ★★ 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-ala264 (accessed [today's date]).

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