Is WAS p.Pro459= (c.1377A>G) pathogenic?

WAS p.Pro459= (c.1377A>G) is classified Likely benign in WAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-12). Very rare (popmax 0.00174%, afr); Associated with Wiskott-Aldrich syndrome.

What condition is associated with WAS p.Pro459= (c.1377A>G)?

WAS p.Pro459= (c.1377A>G) is associated with Wiskott-Aldrich syndrome, X-linked severe congenital neutropenia, thrombocytopenia 1 (ClinVar).

How common is WAS p.Pro459= (c.1377A>G) in the general population?

WAS p.Pro459= (c.1377A>G) is very rare (popmax 0.00174%, afr) (gnomAD).

How is Wiskott-Aldrich syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

WAS p.Pro459=

c.1377A>G · VCV3748381

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00174%, afr)

Conditions

Wiskott-Aldrich syndrome

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 -2.2	GERP -1.1
Overall
CADD	5.181	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00174% African / African-American · 1/57,536 alleles

Overall 8.27e-05% 1/1,209,007 alleles · very rare exomes 1/1,096,024 · genomes 0/112,983 · 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.Pro459=
Coding: c.1377A>G
MANE Select: NM_000377
Type: single nucleotide variant
Location: chrX:48689358 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 459: the 'disordered' region

Full WAS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Wiskott-Aldrich syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: X-linked severe congenital neutropenia thrombocytopenia 1

For Wiskott-Aldrich syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

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-pro459 (accessed [today's date]).

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