Is WEE2 p.Arg542Ser (c.1626A>C) pathogenic?

WEE2 p.Arg542Ser (c.1626A>C) is classified Uncertain significance in WEE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-16). AlphaMissense: likely benign (0.1714); Ultra-rare (popmax 0.0133%, afr).

How common is WEE2 p.Arg542Ser (c.1626A>C) in the general population?

WEE2 p.Arg542Ser (c.1626A>C) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

What do computational predictors say about WEE2 p.Arg542Ser (c.1626A>C)?

AlphaMissense predicts likely benign (score 0.1714) — an in-silico prediction, not a clinical call.

WEE2 p.Arg542Ser

c.1626A>C · rs374519552 · VCV3190455

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1714 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1714	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -5.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.59	GERP 0.33, phastCons 0.46
Regional constraint	o/e 0.92	unconstrained · MANE · 22 kb · p 0.042 · regional, not allelic
Overall
CADD	9.454	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 0.0133% African / African-American · 10/74,928 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.000743% 12/1,614,030 alleles · ultra-rare exomes 3/1,461,848 · genomes 9/152,182 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0133%	7,493
Remaining individualsnot grpmax-eligible	0.0032%	31,241

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.Arg542Ser
Coding: c.1626A>C
MANE Select: NM_001105558
dbSNP: rs374519552
Type: single nucleotide variant
Location: chr7:141729621 (GRCh38)
Gene constraint: LOEUF 1.031 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.50 · 1 PDB
Residue 542: the 'disordered' region

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-arg542ser (accessed [today's date]).

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