Is WAS p.Arg138fs (c.412dup) pathogenic?

WAS p.Arg138fs (c.412dup) is classified Pathogenic in WAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-17). No gnomAD frequency available for this variant; Associated with X-linked severe congenital neutropenia.

What condition is associated with WAS p.Arg138fs (c.412dup)?

WAS p.Arg138fs (c.412dup) is associated with X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome, thrombocytopenia 1 (ClinVar).

How common is WAS p.Arg138fs (c.412dup) in the general population?

WAS p.Arg138fs (c.412dup) is no gnomAD frequency available for this variant (gnomAD).

How is X-linked severe congenital neutropenia inherited?

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

WAS p.Arg138fs

c.412dup · rs2519280880 · VCV2029720

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

X-linked severe congenital neutropenia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: WAS
Protein: p.Arg138fs
Coding: c.412dup
MANE Select: NM_000377
dbSNP: rs2519280880
Type: Duplication
Location: chrX:48685783 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 138: the wh1 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.Arg138Pro Pathogenic ★★ same residue
WAS p.Arg138Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
WAS p.Arg138Trp Uncertain significance ★ ⚠ same residue
WAS p.Arg13fs Pathogenic ★★ same condition
WAS p.Pro402_Pro404dup Uncertain significance ★★ same condition
WAS c.273+10_273+11dup Benign/Likely benign ★★ same condition
WAS c.273+11dup Benign/Likely benign ★★ same condition
WAS c.273+9_273+11dup Likely benign ★★ 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-arg138fs (accessed [today's date]).

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