Is WAS p.Pro176Ser (c.526C>T) pathogenic?

WAS p.Pro176Ser (c.526C>T) is classified Uncertain significance in WAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-02). AlphaMissense: likely benign (0.0682); Very rare (popmax 0.00295%, eas); Associated with Inborn genetic diseases.

What condition is associated with WAS p.Pro176Ser (c.526C>T)?

WAS p.Pro176Ser (c.526C>T) is associated with Inborn genetic diseases (ClinVar).

How common is WAS p.Pro176Ser (c.526C>T) in the general population?

WAS p.Pro176Ser (c.526C>T) is very rare (popmax 0.00295%, eas) (gnomAD).

What do computational predictors say about WAS p.Pro176Ser (c.526C>T)?

AlphaMissense predicts likely benign (score 0.0682) — an in-silico prediction, not a clinical call.

WAS p.Pro176Ser

c.526C>T · VCV3468954

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0682 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00295%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0682	likely benign
REVEL	0.452	indeterminate
SaProt	LLR -7.97	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.3, phastCons 1
Regional constraint	o/e 1.55	unconstrained · MANE · 276 bp · p 0.014 · regional, not allelic
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00295% East Asian · 1/33,877 alleles

Overall 8.25e-05% 1/1,212,155 alleles · very rare exomes 1/1,098,153 · genomes 0/114,002 · 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.Pro176Ser
Coding: c.526C>T
MANE Select: NM_000377
Type: single nucleotide variant
Location: chrX:48686101 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 176: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

WAS p.Arg328Gln Uncertain significance ★★ ⚠ same condition
WAS p.Arg377Cys Uncertain significance ★★ ⚠ same condition
WAS p.Arg94Gln Uncertain significance ★★ ⚠ same condition
WAS p.Asp489Gly Uncertain significance ★★ ⚠ same condition
WAS p.Pro386Ser Uncertain significance ★★ ⚠ same condition
WAS p.Thr282Ala Uncertain significance ★★ ⚠ same condition
WAS p.Arg157His Likely benign ★★ same condition
WAS p.Pro192Leu Likely benign ★★ 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-pro176ser (accessed [today's date]).

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