Is WAC p.Ser286fs (c.854dup) pathogenic?

WAC p.Ser286fs (c.854dup) is classified Pathogenic in WAC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-14).

WAC p.Ser286fs

c.854dup · VCV3364223

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 7 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1

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

Variant & gene context

Gene: WAC
Protein: p.Ser286fs
Coding: c.854dup
MANE Select: NM_016628
Type: Duplication
Location: chr10:28595975 (GRCh38)
Gene constraint: LOEUF 0.248 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.71
Residue 286: the 'disordered' region; a UniProt-annotated variant site (found in a patient with severe intellectual disability; likely pathogenic)

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

Similar variants

WAC p.Ser286Tyr Uncertain significance ★ ⚠ same residue
WAC p.Ala201fs Likely pathogenic ★ same type
WAC p.Ala285fs Pathogenic ★ same type
WAC p.Arg47fs Likely pathogenic ★ same type
WAC p.Arg622fs Pathogenic ★ same type
WAC p.Asp126fs Pathogenic ★ same type
WAC p.Asp502Ter Pathogenic ★ same type
WAC p.Gln156fs 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/wac-p-ser286fs (accessed [today's date]).

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