Is WAS p.Pro112Arg (c.335C>G) pathogenic?

WAS p.Pro112Arg (c.335C>G) is classified Uncertain significance in WAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-19). AlphaMissense: likely benign (0.0801); Very rare (popmax 0.000225%, nfe); Associated with thrombocytopenia 1.

What condition is associated with WAS p.Pro112Arg (c.335C>G)?

WAS p.Pro112Arg (c.335C>G) is associated with thrombocytopenia 1, X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome (ClinVar).

How common is WAS p.Pro112Arg (c.335C>G) in the general population?

WAS p.Pro112Arg (c.335C>G) is very rare (popmax 0.000225%, nfe) (gnomAD).

What do computational predictors say about WAS p.Pro112Arg (c.335C>G)?

AlphaMissense predicts likely benign (score 0.0801) — an in-silico prediction, not a clinical call.

WAS p.Pro112Arg

c.335C>G · rs1458417951 · VCV2179171

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0801 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000225%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

thrombocytopenia 1

Computational evidence

Protein change
AlphaMissense	0.0801	likely benign
REVEL	0.49	indeterminate
SaProt	LLR -10.35	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 0.49, phastCons 0.45
Regional constraint	o/e 0.52	unconstrained · MANE · 1,973 bp · p 1.3e-07 · regional, not allelic
Overall
CADD	18.22	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 0.000225% European (non-Finnish) · 2/890,508 alleles

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

Overall 0.000167% 2/1,200,503 alleles · very rare exomes 1/1,088,625 · genomes 1/111,878 · 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.Pro112Arg
Coding: c.335C>G
MANE Select: NM_000377
dbSNP: rs1458417951
Type: single nucleotide variant
Location: chrX:48685608 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 112: 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.Pro112His Uncertain significance ★ ⚠ 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-pro112arg (accessed [today's date]).

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