Is WAS p.Pro354= (c.1062A>C) pathogenic?

WAS p.Pro354= (c.1062A>C) is classified Likely benign in WAS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-01). Very rare (popmax 0.00347%, eas); Associated with X-linked severe congenital neutropenia.

What condition is associated with WAS p.Pro354= (c.1062A>C)?

WAS p.Pro354= (c.1062A>C) is associated with X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome, thrombocytopenia 1 (ClinVar).

How common is WAS p.Pro354= (c.1062A>C) in the general population?

WAS p.Pro354= (c.1062A>C) is very rare (popmax 0.00347%, eas) (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.Pro354=

c.1062A>C · rs1602179326 · VCV2929561

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00347%, eas)

Conditions

X-linked severe congenital neutropenia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.9	GERP -0.95, phastCons 0.026
Overall
CADD	3.749	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00347% East Asian · 1/28,779 alleles

Filtering AF 0.000271% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000178%

Overall 0.00105% 11/1,045,683 alleles · very rare exomes 10/957,507 · genomes 1/88,176 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00537%	18,620
East Asiangrpmax	0.00347%	28,779
Admixed American	0.00308%	32,474
African / African-American	0.00216%	46,287
European (non-Finnish)	0.000754%	132,669

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro354=
Coding: c.1062A>C
MANE Select: NM_000377
dbSNP: rs1602179326
Type: single nucleotide variant
Location: chrX:48688790 (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.Pro354Gln Uncertain significance ★ ⚠ same residue
WAS p.Pro354fs Pathogenic ★ same residue
WAS p.Pro354del Conflicting classifications of pathogenicity ★ 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

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-pro354 (accessed [today's date]).

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