Is WAS p.Ser242Arg (c.726T>G) pathogenic?

WAS p.Ser242Arg (c.726T>G) is classified Uncertain significance in WAS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-28). AlphaMissense: likely pathogenic (0.9361); Very rare (popmax 0.00352%, afr); Associated with X-linked severe congenital neutropenia.

What condition is associated with WAS p.Ser242Arg (c.726T>G)?

WAS p.Ser242Arg (c.726T>G) is associated with X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome, thrombocytopenia 1 (ClinVar).

How common is WAS p.Ser242Arg (c.726T>G) in the general population?

WAS p.Ser242Arg (c.726T>G) is very rare (popmax 0.00352%, afr) (gnomAD).

How is X-linked severe congenital neutropenia inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about WAS p.Ser242Arg (c.726T>G)?

AlphaMissense predicts likely pathogenic (score 0.9361) — an in-silico prediction, not a clinical call.

WAS p.Ser242Arg

c.726T>G · rs947162120 · VCV1003460

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9361 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00352%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

X-linked severe congenital neutropenia

Computational evidence

Protein change
AlphaMissense	0.9361	likely pathogenic · top 10% in WAS
REVEL	0.526	indeterminate
SaProt	LLR -6.55	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.13	GERP -1.7, phastCons 0.99
Regional constraint	o/e 0.56	unconstrained · MANE · 2,597 bp · p 6e-07 · regional, not allelic
Overall
CADD	21.6	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 0.00352% African / African-American · 2/56,893 alleles

Filtering AF 0.000583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000218%

Overall 0.000166% 2/1,201,784 alleles · very rare exomes 0/1,090,514 · genomes 2/111,270 · joint denominator

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: WAS
Protein: p.Ser242Arg
Coding: c.726T>G
MANE Select: NM_000377
dbSNP: rs947162120
Type: single nucleotide variant
Location: chrX:48686947 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 242: the crib domain

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

Disease context

X-linked severe congenital neutropenia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Wiskott-Aldrich syndrome thrombocytopenia 1

For X-linked severe congenital neutropenia (Orphanet):

Inheritance: X-linked recessive
Onset: Infancy, Neonatal

Similar variants

WAS p.Ser242Cys Benign/Likely benign ★★ same residue
WAS p.Ser242fs Pathogenic/Likely pathogenic ★★ same residue
WAS c.1339-2A>G Pathogenic/Likely pathogenic ★★ same condition
WAS c.1453+2T>C Pathogenic ★★ same condition
WAS c.273+1G>A Pathogenic ★★ same condition
WAS c.360+1G>A Pathogenic ★★ same condition
WAS c.559+5G>A Pathogenic ★★ same condition
WAS c.777+1G>A Pathogenic ★★ same condition

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/was-p-ser242arg (accessed [today's date]).

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