Is WAS p.Pro370= (c.1110A>C) pathogenic?

WAS p.Pro370= (c.1110A>C) is classified Likely benign in WAS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). Rare (popmax 0.316%, eas); Associated with X-linked severe congenital neutropenia.

What condition is associated with WAS p.Pro370= (c.1110A>C)?

WAS p.Pro370= (c.1110A>C) is associated with X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome, thrombocytopenia 1 (ClinVar).

How common is WAS p.Pro370= (c.1110A>C) in the general population?

WAS p.Pro370= (c.1110A>C) is rare (popmax 0.316%, 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.Pro370=

c.1110A>C · rs782244198 · VCV695313

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.316%, 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	<0.2	all four deltas below 0.2 · A>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.1	GERP 0.37, phastCons 1
Overall
CADD	12.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.316% East Asian · 47/14,871 alleles

Filtering AF 0.244% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.219%

Overall 0.0126% 101/803,533 alleles · rare exomes 86/749,950 · genomes 15/53,583 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.316%	316
South Asian	0.0862%	1,160
Remaining individualsnot grpmax-eligible	0.0239%	4,191
Admixed American	0.0127%	7,890
Ashkenazi Jewishnot grpmax-eligible	0.00879%	11,383
African / African-American	0.00621%	16,098
Finnishnot grpmax-eligible	0.0042%	23,833
European (non-Finnish)	0.0022%	45,417

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.Pro370=
Coding: c.1110A>C
MANE Select: NM_000377
dbSNP: rs782244198
Type: single nucleotide variant
Location: chrX:48688838 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 370: 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 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
WAS p.Ala56Val 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-pro370 (accessed [today's date]).

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