Is WAS p.Ter503= (c.1508G>A) pathogenic?

WAS p.Ter503= (c.1508G>A) is classified Likely benign in WAS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-10). Very rare (popmax 0.0022%, amr); Associated with thrombocytopenia 1.

What condition is associated with WAS p.Ter503= (c.1508G>A)?

WAS p.Ter503= (c.1508G>A) is associated with thrombocytopenia 1, X-linked severe congenital neutropenia, Wiskott-Aldrich syndrome (ClinVar).

How common is WAS p.Ter503= (c.1508G>A) in the general population?

WAS p.Ter503= (c.1508G>A) is very rare (popmax 0.0022%, amr) (gnomAD).

WAS p.Ter503=

c.1508G>A · rs1241403780 · VCV2418082

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0022%, amr)

Conditions

thrombocytopenia 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function in a haploinsufficient gene (ClinGen)
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -1.8, phastCons 1
Overall
CADD	7.308	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% Admixed American · 1/45,449 alleles

Filtering AF 8.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000331% 4/1,207,671 alleles · very rare exomes 2/1,097,716 · genomes 2/109,955 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0022%	45,449
European (non-Finnish)	0.000335%	298,131

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.Ter503=
Coding: c.1508G>A
MANE Select: NM_000377
dbSNP: rs1241403780
Type: single nucleotide variant
Location: chrX:48691161 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB

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.Ter503Arg Likely pathogenic ★ same residue
WAS p.Ter503Ser Uncertain significance ★ same residue
WAS p.Ter503Trp Uncertain significance ★ same residue
WAS p.Ter503CysextTer? 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

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-ter503 (accessed [today's date]).

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