Is WEE1 p.Ser85Arg (c.253A>C) pathogenic?

WEE1 p.Ser85Arg (c.253A>C) is classified Uncertain significance in WEE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-05). AlphaMissense: likely benign (0.1601); Absent from gnomAD v4.1.

How common is WEE1 p.Ser85Arg (c.253A>C) in the general population?

WEE1 p.Ser85Arg (c.253A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about WEE1 p.Ser85Arg (c.253A>C)?

AlphaMissense predicts likely benign (score 0.1601) — an in-silico prediction, not a clinical call.

WEE1 p.Ser85Arg

c.253A>C · rs2494216664 · VCV2363779

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1601 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,167,036)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1601	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -7.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 2,554 bp · p 0.39 · regional, not allelic
Overall
CADD	20.9	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

No allele count reported in gnomAD v4.1 (AN 1,167,036). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: WEE1
Protein: p.Ser85Arg
Coding: c.253A>C
MANE Select: NM_003390
dbSNP: rs2494216664
Type: single nucleotide variant
Location: chr11:9574186 (GRCh38)
Gene constraint: LOEUF 0.405 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.90 · 29 PDB
Residue 85: a modified residue (phosphoserine); the 'disordered' region

Full WEE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

WEE1 p.Gly210Cys Benign ★★ same type
WEE1 p.Ala130Val Uncertain significance ★ ⚠ same type
WEE1 p.Ala156Thr Uncertain significance ★ ⚠ same type
WEE1 p.Ala15Ser Uncertain significance ★ ⚠ same type
WEE1 p.Ala387Ser Uncertain significance ★ ⚠ same type
WEE1 p.Ala510Thr Uncertain significance ★ ⚠ same type
WEE1 p.Arg13Cys Uncertain significance ★ ⚠ same type
WEE1 p.Arg223Gly 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/wee1-p-ser85arg (accessed [today's date]).

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