Is WAS p.Asp485= (c.1455C>T) pathogenic?

WAS p.Asp485= (c.1455C>T) is classified Conflicting classifications of pathogenicity in WAS (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-02). Ultra-rare (popmax 0.0707%, afr); Associated with thrombocytopenia 1.

What condition is associated with WAS p.Asp485= (c.1455C>T)?

WAS p.Asp485= (c.1455C>T) is associated with thrombocytopenia 1, X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome (ClinVar).

How common is WAS p.Asp485= (c.1455C>T) in the general population?

WAS p.Asp485= (c.1455C>T) is ultra-rare (popmax 0.0707%, afr) (gnomAD).

WAS p.Asp485=

c.1455C>T · rs35359501 · VCV547079

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0707%, 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	all four deltas below 0.2 · C>A here scores Δ0.87 · evaluated, not missing
Constraint at this position
Conservation	phyloP -9.9	GERP -2.6
Overall
CADD	0.351	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0707% African / African-American · 40/56,549 alleles

Filtering AF 0.0533% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0473%

Overall 0.00431% 52/1,207,470 alleles · ultra-rare exomes 32/1,097,472 · genomes 20/109,998 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0707%	1,414
Middle Eastern	0.023%	4,345
Remaining individualsnot grpmax-eligible	0.00631%	15,847
East Asian	0.00593%	16,851
South Asian	0.00176%	56,664
European (non-Finnish)	0.000559%	178,836

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.Asp485=
Coding: c.1455C>T
MANE Select: NM_000377
dbSNP: rs35359501
Type: single nucleotide variant
Location: chrX:48691108 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 485: 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.Asp485Asn Pathogenic ★★ 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-asp485 (accessed [today's date]).

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