Is WAS p.Arg86Pro (c.257G>C) pathogenic?

WAS p.Arg86Pro (c.257G>C) is classified Likely pathogenic in WAS (ClinVar, Single submitter, 1 submitter; last evaluated 2017-09-13). AlphaMissense: likely pathogenic (0.9963); Absent from gnomAD v4.1; Associated with Wiskott-Aldrich syndrome.

What condition is associated with WAS p.Arg86Pro (c.257G>C)?

WAS p.Arg86Pro (c.257G>C) is associated with Wiskott-Aldrich syndrome (ClinVar).

How common is WAS p.Arg86Pro (c.257G>C) in the general population?

WAS p.Arg86Pro (c.257G>C) 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.Arg86Pro (c.257G>C)?

AlphaMissense predicts likely pathogenic (score 0.9963) — an in-silico prediction, not a clinical call.

WAS p.Arg86Pro

c.257G>C · rs132630268 · VCV633021

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9963 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Wiskott-Aldrich syndrome

Computational evidence

Protein change
AlphaMissense	0.9963	likely pathogenic ✓ concordant with ClinVar · top 2% in WAS
REVEL	0.924	moderately pathogenic-leaning
SaProt	LLR -16.87	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 12	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	30.0	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.Arg86Pro
Coding: c.257G>C
MANE Select: NM_000377
dbSNP: rs132630268
Type: single nucleotide variant
Location: chrX:48684407 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 86: the wh1 domain; a UniProt-annotated variant site (in was)

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

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.Arg86Cys Pathogenic ★★ same residue
WAS p.Arg86His Pathogenic ★★ same residue
WAS p.Arg86Leu Pathogenic same residue
WAS p.Arg86fs Pathogenic/Likely pathogenic ★★ 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

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-arg86pro (accessed [today's date]).

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