Is WAS p.Pro397= (c.1191G>A) pathogenic?

WAS p.Pro397= (c.1191G>A) is classified Likely benign in WAS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-06-30). Ultra-rare (popmax 0.0539%, afr); Associated with thrombocytopenia 1.

What condition is associated with WAS p.Pro397= (c.1191G>A)?

WAS p.Pro397= (c.1191G>A) is associated with thrombocytopenia 1, X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome (ClinVar).

How common is WAS p.Pro397= (c.1191G>A) in the general population?

WAS p.Pro397= (c.1191G>A) is ultra-rare (popmax 0.0539%, afr) (gnomAD).

WAS p.Pro397=

c.1191G>A · rs782486251 · VCV1597253

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0539%, afr)

Conditions

thrombocytopenia 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -12	GERP -3
Overall
CADD	0.014	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0539% African / African-American · 27/50,083 alleles

Filtering AF 0.038% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0327%

Overall 0.00429% 44/1,025,587 alleles · ultra-rare exomes 24/922,073 · genomes 20/103,514 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0539%	1,855
Remaining individualsnot grpmax-eligible	0.0189%	5,299
Admixed American	0.0118%	8,486
East Asian	0.00475%	21,034
South Asian	0.0042%	23,837
European (non-Finnish)	0.000381%	262,362

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.Pro397=
Coding: c.1191G>A
MANE Select: NM_000377
dbSNP: rs782486251
Type: single nucleotide variant
Location: chrX:48688919 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 397: 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 p.Pro397Leu Uncertain significance ★★ ⚠ same residue
WAS p.Pro397Ala 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

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-pro397 (accessed [today's date]).

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