Is WAS p.Pro372= (c.1116T>A) pathogenic?

WAS p.Pro372= (c.1116T>A) is classified Likely benign in WAS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-22). Ultra-rare (popmax 0.0205%, afr); Associated with X-linked severe congenital neutropenia.

What condition is associated with WAS p.Pro372= (c.1116T>A)?

WAS p.Pro372= (c.1116T>A) is associated with X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome, thrombocytopenia 1 (ClinVar).

How common is WAS p.Pro372= (c.1116T>A) in the general population?

WAS p.Pro372= (c.1116T>A) is ultra-rare (popmax 0.0205%, afr) (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.Pro372=

c.1116T>A · rs1409684725 · VCV2925085

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0205%, afr)

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 0.94	GERP 1.5, phastCons 1
Overall
CADD	9.627	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0205% African / African-American · 5/24,417 alleles

Filtering AF 0.00818% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00739%

Overall 0.0103% 71/689,965 alleles · ultra-rare exomes 64/660,874 · genomes 7/29,091 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0205%	4,883
Admixed American	0.019%	5,269
Ashkenazi Jewishnot grpmax-eligible	0.011%	9,097
European (non-Finnish)	0.0103%	9,702
East Asian	0.00973%	10,277
South Asian	0.00908%	11,009
Remaining individualsnot grpmax-eligible	0.00409%	24,452

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.Pro372=
Coding: c.1116T>A
MANE Select: NM_000377
dbSNP: rs1409684725
Type: single nucleotide variant
Location: chrX:48688844 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 372: 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-pro372 (accessed [today's date]).

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