Is WAS p.Arg138Pro (c.413G>C) pathogenic?

WAS p.Arg138Pro (c.413G>C) is classified Pathogenic in WAS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-04). AlphaMissense: likely pathogenic (0.6868); Absent from gnomAD v4.1; Associated with thrombocytopenia 1.

What condition is associated with WAS p.Arg138Pro (c.413G>C)?

WAS p.Arg138Pro (c.413G>C) is associated with thrombocytopenia 1 (ClinVar).

How common is WAS p.Arg138Pro (c.413G>C) in the general population?

WAS p.Arg138Pro (c.413G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about WAS p.Arg138Pro (c.413G>C)?

AlphaMissense predicts likely pathogenic (score 0.6868) — an in-silico prediction, not a clinical call.

WAS p.Arg138Pro

c.413G>C · rs139265251 · VCV495847

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6868 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

thrombocytopenia 1

Computational evidence

Protein change
AlphaMissense	0.6868	likely pathogenic ✓ concordant with ClinVar
REVEL	0.589	indeterminate
SaProt	LLR -14.00	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.023	GERP -3.1, phastCons 0.12
Regional constraint	o/e 0.52	unconstrained · MANE · 1,973 bp · p 1.3e-07 · regional, not allelic
Overall
CADD	17.86	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.Arg138Pro
Coding: c.413G>C
MANE Select: NM_000377
dbSNP: rs139265251
Type: single nucleotide variant
Location: chrX:48685786 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 138: 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

Similar variants

WAS p.Arg138Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
WAS p.Arg138Trp Uncertain significance ★ ⚠ same residue
WAS p.Arg138fs Pathogenic ★ same residue
WAS c.1339-2A>G Pathogenic/Likely 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

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-arg138pro (accessed [today's date]).

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