Is WAS p.Pro399= (c.1197A>G) pathogenic?

WAS p.Pro399= (c.1197A>G) is classified Likely benign in WAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-18). Very rare (popmax 0.000354%, nfe); Associated with X-linked severe congenital neutropenia.

What condition is associated with WAS p.Pro399= (c.1197A>G)?

WAS p.Pro399= (c.1197A>G) is associated with X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome, thrombocytopenia 1 (ClinVar).

How common is WAS p.Pro399= (c.1197A>G) in the general population?

WAS p.Pro399= (c.1197A>G) is very rare (popmax 0.000354%, nfe) (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.Pro399=

c.1197A>G · rs1602179584 · VCV699162

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000354%, nfe)

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 -1.4	GERP -2.6
Overall
CADD	0.368	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000354% European (non-Finnish) · 3/847,179 alleles

Filtering AF 9.4e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.6e-05%

Overall 0.000269% 3/1,116,873 alleles · very rare exomes 3/1,016,049 · genomes 0/100,824 · joint denominator

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.Pro399=
Coding: c.1197A>G
MANE Select: NM_000377
dbSNP: rs1602179584
Type: single nucleotide variant
Location: chrX:48688925 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 399: 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.Pro399Arg 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-pro399 (accessed [today's date]).

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