Is WAC p.Pro36fs (c.105_106insGA) pathogenic?

WAC p.Pro36fs (c.105106insGA) is classified Likely pathogenic in WAC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-27). Associated with DeSanto-Shinawi syndrome due to WAC point mutation.

What condition is associated with WAC p.Pro36fs (c.105_106insGA)?

WAC p.Pro36fs (c.105_106insGA) is associated with DeSanto-Shinawi syndrome due to WAC point mutation (ClinVar).

WAC p.Pro36fs

c.105_106insGA · VCV4846961

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

DeSanto-Shinawi syndrome due to WAC point mutation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 3 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	phastCons 1

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

Variant & gene context

Gene: WAC
Protein: p.Pro36fs
Coding: c.105_106insGA
MANE Select: NM_016628
Type: Insertion
Location: chr10:28535588 (GRCh38)
Gene constraint: LOEUF 0.248 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.71
Residue 36: the 'disordered' region

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

Disease context

DeSanto-Shinawi syndrome due to WAC point mutation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

WAC c.1437+1G>A Pathogenic/Likely pathogenic ★★ same condition
WAC c.381+1G>T Likely pathogenic ★★ same condition
WAC p.Arg151Ter Pathogenic ★★ same condition
WAC p.Arg47Ter Pathogenic ★★ same condition
WAC p.Arg513Ter Pathogenic ★★ same condition
WAC p.Arg550Ter Pathogenic ★★ same condition
WAC p.Arg613Ter Pathogenic/Likely pathogenic ★★ same condition
WAC p.Arg622Ter Pathogenic/Likely 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/wac-p-pro36fs (accessed [today's date]).

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