Is WAS p.Ala418Ser (c.1252G>T) pathogenic?

WAS p.Ala418Ser (c.1252G>T) is classified Benign in WAS (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-16). AlphaMissense: likely benign (0.0683); Ultra-rare (popmax 0.0116%, amr); Associated with X-linked severe congenital neutropenia.

What condition is associated with WAS p.Ala418Ser (c.1252G>T)?

WAS p.Ala418Ser (c.1252G>T) is associated with X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome, thrombocytopenia 1 (ClinVar).

How common is WAS p.Ala418Ser (c.1252G>T) in the general population?

WAS p.Ala418Ser (c.1252G>T) is ultra-rare (popmax 0.0116%, 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.Ala418Ser (c.1252G>T)?

AlphaMissense predicts likely benign (score 0.0683) — an in-silico prediction, not a clinical call.

WAS p.Ala418Ser

c.1252G>T · rs782784813 · VCV833892

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0683 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0116%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked severe congenital neutropenia

Computational evidence

Protein change
AlphaMissense	0.0683	likely benign
REVEL	0.218	benign-leaning
SaProt	LLR -5.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.45	GERP -3.1
Regional constraint	o/e 0.90	unconstrained · MANE · 2,456 bp · p 0.22 · regional, not allelic
Overall
CADD	0.165	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 0.0116% Admixed American · 5/42,985 alleles

Filtering AF 0.0045% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00296%

Overall 0.00345% 41/1,189,909 alleles · ultra-rare exomes 39/1,078,134 · genomes 2/111,775 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0116%	8,597
Remaining individualsnot grpmax-eligible	0.00854%	11,707
European (non-Finnish)	0.0035%	28,570
African / African-American	0.00176%	56,775

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.Ala418Ser
Coding: c.1252G>T
MANE Select: NM_000377
dbSNP: rs782784813
Type: single nucleotide variant
Location: chrX:48688980 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 418: 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.Ala418Val Likely benign ★★ same residue
WAS p.Ala418Thr 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-ala418ser (accessed [today's date]).

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