Is WAS p.His30= (c.90C>T) pathogenic?

WAS p.His30= (c.90C>T) is classified Benign/Likely benign in WAS (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-28). Rare (popmax 0.206%, mid); Associated with X-linked severe congenital neutropenia.

What condition is associated with WAS p.His30= (c.90C>T)?

WAS p.His30= (c.90C>T) is associated with X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome, thrombocytopenia 1 (ClinVar).

How common is WAS p.His30= (c.90C>T) in the general population?

WAS p.His30= (c.90C>T) is rare (popmax 0.206%, mid) (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.His30=

c.90C>T · rs148800063 · VCV458506

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.206%, mid)

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 -3.5	GERP -2.3
Overall
CADD	2.437	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.206% Middle Eastern · 9/4,373 alleles

Filtering AF 0.113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.111%

Overall 0.0968% 1,171/1,209,192 alleles · rare exomes 1,106/1,098,247 · genomes 65/110,945 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.206%	486
European (non-Finnish)	0.119%	837
Remaining individualsnot grpmax-eligible	0.0798%	1,252
South Asian	0.0599%	1,670
African / African-American	0.0193%	5,169
Finnishnot grpmax-eligible	0.0108%	9,299
Ashkenazi Jewishnot grpmax-eligible	0.00908%	11,014
Admixed American	0.00657%	15,221

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.His30=
Coding: c.90C>T
MANE Select: NM_000377
dbSNP: rs148800063
Type: single nucleotide variant
Location: chrX:48683943 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 30: a UniProt-annotated variant site (in thc1)

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.His30del Uncertain significance ★ 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
WAS c.778-6G>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-his30 (accessed [today's date]).

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