Is WAS p.Phe117= (c.351C>T) pathogenic?

WAS p.Phe117= (c.351C>T) is classified Likely benign in WAS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-15). Very rare (popmax 0.00631%, nfe); Associated with X-linked severe congenital neutropenia.

What condition is associated with WAS p.Phe117= (c.351C>T)?

WAS p.Phe117= (c.351C>T) is associated with X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome, thrombocytopenia 1 (ClinVar).

How common is WAS p.Phe117= (c.351C>T) in the general population?

WAS p.Phe117= (c.351C>T) is very rare (popmax 0.00631%, nfe) (gnomAD).

How is X-linked severe congenital neutropenia inherited?

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

WAS p.Phe117=

c.351C>T · rs143299151 · VCV508428

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00631%, nfe)

Conditions

X-linked severe congenital neutropenia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.61 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.5	GERP -3.1
Overall
CADD	3.37	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00631% European (non-Finnish) · 56/888,073 alleles

Filtering AF 0.00498% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00447%

Overall 0.00518% 62/1,196,289 alleles · very rare exomes 53/1,084,581 · genomes 9/111,708 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00631%	15,858
South Asian	0.0055%	18,185
Remaining individualsnot grpmax-eligible	0.00425%	23,524
Admixed American	0.00224%	44,641

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.Phe117=
Coding: c.351C>T
MANE Select: NM_000377
dbSNP: rs143299151
Type: single nucleotide variant
Location: chrX:48685624 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 117: the wh1 domain

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 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-phe117 (accessed [today's date]).

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