Is WAS p.Pro448Ser (c.1342C>T) pathogenic?

WAS p.Pro448Ser (c.1342C>T) is classified Uncertain significance in WAS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-14). AlphaMissense: likely benign (0.0867); Absent from gnomAD v4.1; Associated with Wiskott-Aldrich syndrome.

What condition is associated with WAS p.Pro448Ser (c.1342C>T)?

WAS p.Pro448Ser (c.1342C>T) is associated with Wiskott-Aldrich syndrome, X-linked severe congenital neutropenia, thrombocytopenia 1 (ClinVar).

How common is WAS p.Pro448Ser (c.1342C>T) in the general population?

WAS p.Pro448Ser (c.1342C>T) is absent from gnomAD v4.1 (gnomAD).

How is Wiskott-Aldrich syndrome inherited?

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

What do computational predictors say about WAS p.Pro448Ser (c.1342C>T)?

AlphaMissense predicts likely benign (score 0.0867) — an in-silico prediction, not a clinical call.

WAS p.Pro448Ser

c.1342C>T · rs2519288817 · VCV2112158

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0867 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Wiskott-Aldrich syndrome

Computational evidence

Protein change
AlphaMissense	0.0867	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -5.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.33, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 2,456 bp · p 0.22 · regional, not allelic
Overall
CADD	10.51	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: WAS
Protein: p.Pro448Ser
Coding: c.1342C>T
MANE Select: NM_000377
dbSNP: rs2519288817
Type: single nucleotide variant
Location: chrX:48689323 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 448: 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 p.Pro448Leu 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-pro448ser (accessed [today's date]).

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