Is WAS p.Leu101Pro (c.302T>C) pathogenic?

WAS p.Leu101Pro (c.302T>C) is classified Pathogenic in WAS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-17). AlphaMissense: likely pathogenic (0.9244); Absent from gnomAD v4.1; Associated with thrombocytopenia 1.

What condition is associated with WAS p.Leu101Pro (c.302T>C)?

WAS p.Leu101Pro (c.302T>C) is associated with thrombocytopenia 1, X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome (ClinVar).

How common is WAS p.Leu101Pro (c.302T>C) in the general population?

WAS p.Leu101Pro (c.302T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about WAS p.Leu101Pro (c.302T>C)?

AlphaMissense predicts likely pathogenic (score 0.9244) — an in-silico prediction, not a clinical call.

WAS p.Leu101Pro

c.302T>C · rs2519280132 · VCV2138568

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9244 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

thrombocytopenia 1

Computational evidence

Protein change
AlphaMissense	0.9244	likely pathogenic ✓ concordant with ClinVar
REVEL	0.913	moderately pathogenic-leaning
SaProt	LLR -15.99	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 1,973 bp · p 1.3e-07 · regional, not allelic
Overall
CADD	25.8	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.Leu101Pro
Coding: c.302T>C
MANE Select: NM_000377
dbSNP: rs2519280132
Type: single nucleotide variant
Location: chrX:48685575 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 101: the wh1 domain

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

Disease context

thrombocytopenia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: X-linked severe congenital neutropenia Wiskott-Aldrich syndrome

Similar variants

WAS p.Leu101= Likely benign ★ 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-leu101pro (accessed [today's date]).

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