Is WAS p.Ser24Pro (c.70T>C) pathogenic?

WAS p.Ser24Pro (c.70T>C) is classified Pathogenic in WAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-23). AlphaMissense: likely pathogenic (0.9561); Absent from gnomAD v4.1; Associated with X-linked severe congenital neutropenia.

What condition is associated with WAS p.Ser24Pro (c.70T>C)?

WAS p.Ser24Pro (c.70T>C) is associated with X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome, thrombocytopenia 1 (ClinVar).

How common is WAS p.Ser24Pro (c.70T>C) in the general population?

WAS p.Ser24Pro (c.70T>C) is absent from gnomAD v4.1 (gnomAD).

How is X-linked severe congenital neutropenia inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about WAS p.Ser24Pro (c.70T>C)?

AlphaMissense predicts likely pathogenic (score 0.9561) — an in-silico prediction, not a clinical call.

WAS p.Ser24Pro

c.70T>C · rs2062410722 · VCV834695

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9561 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked severe congenital neutropenia

Computational evidence

Protein change
AlphaMissense	0.9561	likely pathogenic ✓ concordant with ClinVar · top 8% in WAS
REVEL	0.788	moderately pathogenic-leaning
SaProt	LLR -9.72	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 1,973 bp · p 1.3e-07 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

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.Ser24Pro
Coding: c.70T>C
MANE Select: NM_000377
dbSNP: rs2062410722
Type: single nucleotide variant
Location: chrX:48683923 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB

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-ser24pro (accessed [today's date]).

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