Is WAS p.Arg86Cys (c.256C>T) pathogenic?

WAS p.Arg86Cys (c.256C>T) is classified Pathogenic in WAS (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-06). AlphaMissense: ambiguous (0.3751); Very rare (popmax 0.000224%, nfe); Associated with Wiskott-Aldrich syndrome.

What condition is associated with WAS p.Arg86Cys (c.256C>T)?

WAS p.Arg86Cys (c.256C>T) is associated with Wiskott-Aldrich syndrome, X-linked severe congenital neutropenia, thrombocytopenia 1 (ClinVar).

How common is WAS p.Arg86Cys (c.256C>T) in the general population?

WAS p.Arg86Cys (c.256C>T) is very rare (popmax 0.000224%, nfe) (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.Arg86Cys (c.256C>T)?

AlphaMissense predicts ambiguous (score 0.3751) — an in-silico prediction, not a clinical call.

WAS p.Arg86Cys

c.256C>T · rs2062412810 · VCV936334

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.3751 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000224%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Wiskott-Aldrich syndrome

Computational evidence

Protein change
AlphaMissense	0.3751	ambiguous
REVEL	0.951	strongly pathogenic-leaning
SaProt	LLR -15.04	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	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	26.2	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

Grpmax group 0.000224% European (non-Finnish) · 2/894,411 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000165% 2/1,209,111 alleles · very rare exomes 2/1,096,161 · genomes 0/112,950 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: WAS
Protein: p.Arg86Cys
Coding: c.256C>T
MANE Select: NM_000377
dbSNP: rs2062412810
Type: single nucleotide variant
Location: chrX:48684406 (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

Also linked: X-linked severe congenital neutropenia thrombocytopenia 1

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.Arg86His Pathogenic ★★ same residue
WAS p.Arg86Pro Likely 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-arg86cys (accessed [today's date]).

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