Is WAS p.Pro395Ala (c.1183C>G) pathogenic?

WAS p.Pro395Ala (c.1183C>G) is classified Uncertain significance in WAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: likely benign (0.0691); Very rare (popmax 0.000116%, nfe); Associated with thrombocytopenia 1.

What condition is associated with WAS p.Pro395Ala (c.1183C>G)?

WAS p.Pro395Ala (c.1183C>G) is associated with thrombocytopenia 1, X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome (ClinVar).

How common is WAS p.Pro395Ala (c.1183C>G) in the general population?

WAS p.Pro395Ala (c.1183C>G) is very rare (popmax 0.000116%, nfe) (gnomAD).

What do computational predictors say about WAS p.Pro395Ala (c.1183C>G)?

AlphaMissense predicts likely benign (score 0.0691) — an in-silico prediction, not a clinical call.

WAS p.Pro395Ala

c.1183C>G · VCV4782440

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0691 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000116%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

thrombocytopenia 1

Computational evidence

Protein change
AlphaMissense	0.0691	likely benign
REVEL	0.515	indeterminate
SaProt	LLR -10.47	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP 1.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 2,456 bp · p 0.22 · regional, not allelic
Overall
CADD	12.37	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 0.000116% European (non-Finnish) · 1/864,211 alleles

Overall 8.7e-05% 1/1,149,078 alleles · very rare exomes 0/1,039,101 · genomes 1/109,977 · 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.Pro395Ala
Coding: c.1183C>G
MANE Select: NM_000377
Type: single nucleotide variant
Location: chrX:48688911 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 395: the 'disordered' region

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 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
WAS p.Ala56Val 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-pro395ala (accessed [today's date]).

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