Is WAS p.Pro354fs (c.1058dup) pathogenic?

WAS p.Pro354fs (c.1058dup) is classified Pathogenic in WAS (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-13). Ultra-rare (gnomAD MAF 1.06e-06); Associated with X-linked severe congenital neutropenia.

What condition is associated with WAS p.Pro354fs (c.1058dup)?

WAS p.Pro354fs (c.1058dup) is associated with X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome, thrombocytopenia 1 (ClinVar).

How common is WAS p.Pro354fs (c.1058dup) in the general population?

WAS p.Pro354fs (c.1058dup) is ultra-rare (gnomAD MAF 1.06e-06) (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.Pro354fs

c.1058dup · rs1557007165 · VCV861115

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 1.06e-06)

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 10 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -7.9	GERP -2.7
Region caveats
Repeat context	tandem	(CCCCAC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

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

Population frequency

dbSNP / gnomAD

Global frequency 0.000106% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: WAS
Protein: p.Pro354fs
Coding: c.1058dup
MANE Select: NM_000377
dbSNP: rs1557007165
Type: Duplication
Location: chrX:48688781 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 354: the 'disordered' region

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.Pro354= Likely benign ★★ same residue
WAS p.Pro354del Conflicting classifications of pathogenicity ★ same residue
WAS p.Pro354Gln 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-pro354fs (accessed [today's date]).

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