Is WAS p.Pro58Ser (c.172C>T) pathogenic?

WAS p.Pro58Ser (c.172C>T) is classified Likely pathogenic in WAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-06). AlphaMissense: likely benign (0.1358); Absent from gnomAD v4.1.

How common is WAS p.Pro58Ser (c.172C>T) in the general population?

WAS p.Pro58Ser (c.172C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about WAS p.Pro58Ser (c.172C>T)?

AlphaMissense predicts likely benign (score 0.1358) — an in-silico prediction, not a clinical call.

WAS p.Pro58Ser

c.172C>T · VCV3380921

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1358 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1358	likely benign ⚠ discordant with ClinVar
REVEL	0.771	pathogenic-leaning
SaProt	LLR -11.81	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 1,973 bp · p 1.3e-07 · regional, not allelic
Overall
CADD	23.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: WAS
Protein: p.Pro58Ser
Coding: c.172C>T
MANE Select: NM_000377
Type: single nucleotide variant
Location: chrX:48684322 (GRCh38)
Structure: AlphaFold pLDDT 70.84 · 7 PDB
Residue 58: the wh1 domain; a UniProt-annotated variant site (in was); a UniProt-annotated variant site (in thc1)

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

Similar variants

WAS p.Pro58His Likely pathogenic ★ ⚠ same residue
WAS p.Pro58Thr Pathogenic ★ ⚠ same residue
WAS p.Pro58Arg Pathogenic ⚠ same residue
WAS c.1339-2A>G Pathogenic/Likely pathogenic ★★ same type
WAS c.1453+2T>C Pathogenic ★★ same type
WAS c.273+1G>A Pathogenic ★★ same type
WAS c.360+1G>A Pathogenic ★★ same type
WAS c.360+1G>T Pathogenic/Likely pathogenic ★★ same type

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-pro58ser (accessed [today's date]).

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