Is WAS p.Pro329Ala (c.985C>G) pathogenic?

WAS p.Pro329Ala (c.985C>G) is classified Likely benign in WAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-14). AlphaMissense: likely benign (0.068); Very rare (popmax 0.00232%, amr); Associated with X-linked severe congenital neutropenia.

What condition is associated with WAS p.Pro329Ala (c.985C>G)?

WAS p.Pro329Ala (c.985C>G) is associated with X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome, thrombocytopenia 1 (ClinVar).

How common is WAS p.Pro329Ala (c.985C>G) in the general population?

WAS p.Pro329Ala (c.985C>G) is very rare (popmax 0.00232%, amr) (gnomAD).

How is X-linked severe congenital neutropenia inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about WAS p.Pro329Ala (c.985C>G)?

AlphaMissense predicts likely benign (score 0.068) — an in-silico prediction, not a clinical call.

WAS p.Pro329Ala

c.985C>G · rs1557007136 · VCV528223

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.068 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00232%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

X-linked severe congenital neutropenia

Computational evidence

Protein change
AlphaMissense	0.068	likely benign
REVEL	0.397	indeterminate
SaProt	LLR -9.12	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.1	GERP 1.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 2,456 bp · p 0.22 · regional, not allelic
Overall
CADD	17.08	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 0.00232% Admixed American · 1/43,114 alleles

Overall 8.45e-05% 1/1,183,331 alleles · very rare exomes 1/1,070,486 · genomes 0/112,845 · 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.Pro329Ala
Coding: c.985C>G
MANE Select: NM_000377
dbSNP: rs1557007136
Type: single nucleotide variant
Location: chrX:48688713 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 329: the 'disordered' region

Full WAS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

X-linked severe congenital neutropenia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Wiskott-Aldrich syndrome thrombocytopenia 1

For X-linked severe congenital neutropenia (Orphanet):

Inheritance: X-linked recessive
Onset: Infancy, Neonatal

Similar variants

WAS p.Pro329= Likely benign ★ 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-pro329ala (accessed [today's date]).

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