WAC p.Arg151Ter
c.451C>T · rs886041614 · VCV280400
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
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 | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 5 of 14 |
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 0.93, phastCons 1 |
| Overall | ||
| CADD | 39.0 | 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
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
- WAC
- Protein
- p.Arg151Ter
- Coding
- c.451C>T
- MANE Select
- NM_016628
- dbSNP
- rs886041614
- Type
- single nucleotide variant
- Location
- chr10:28589805 (GRCh38)
- Gene constraint
- LOEUF 0.248 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 55.71
- Residue 151
- the ww domain; a UniProt-annotated variant site (found in a patient with severe intellectual disability; likely pathogenic)
Similar variants
- WAC p.Arg151Gly Uncertain significance ★ ⚠ same residue
- WAC p.Arg151Gln Likely benign ★ same residue
- WAC c.1437+1G>A Pathogenic/Likely pathogenic ★★ same condition
- WAC c.381+1G>T Likely 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
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-arg151ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown