Is WAS p.Cys73Ser (c.217T>A) pathogenic?

WAS p.Cys73Ser (c.217T>A) is classified Uncertain significance in WAS (ClinVar, Single submitter, 1 submitter; last evaluated 2019-02-01). AlphaMissense: ambiguous (0.4521); Absent from gnomAD v4.1; Associated with thrombocytopenia.

What condition is associated with WAS p.Cys73Ser (c.217T>A)?

WAS p.Cys73Ser (c.217T>A) is associated with thrombocytopenia (ClinVar).

How common is WAS p.Cys73Ser (c.217T>A) in the general population?

WAS p.Cys73Ser (c.217T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about WAS p.Cys73Ser (c.217T>A)?

AlphaMissense predicts ambiguous (score 0.4521) — an in-silico prediction, not a clinical call.

WAS p.Cys73Ser

c.217T>A · rs1602176652 · VCV627275

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4521 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

thrombocytopenia

Computational evidence

Protein change
AlphaMissense	0.4521	ambiguous
REVEL	0.85	moderately pathogenic-leaning
SaProt	LLR -10.59	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
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	24.8	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.Cys73Ser
Coding: c.217T>A
MANE Select: NM_000377
dbSNP: rs1602176652
Type: single nucleotide variant
Location: chrX:48684367 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 73: the wh1 domain; a UniProt-annotated variant site (in was; severe form)

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

Disease context

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

Similar variants

WAS p.Cys73Ter Pathogenic ★ same residue
WAS p.Thr45Met Pathogenic ★★ same condition
WAS p.Glu486Lys Uncertain significance ★★ ⚠ same condition
WAS p.Arg268fs Pathogenic ★ same condition
WAS p.His472_Met474del Likely pathogenic ★ same condition
WAS c.1339-2A>G Pathogenic/Likely pathogenic ★★ same type
WAS c.1453+2T>C Pathogenic ★★ same type
WAS c.273+1G>A Pathogenic ★★ same type

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-cys73ser (accessed [today's date]).

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