SHANK3 p.Pro1069fs
c.3206del · VCV4855279
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
Phelan-McDermid syndrome
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 22 of 23 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.3, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- SHANK3
- Protein
- p.Pro1069fs
- Coding
- c.3206del
- MANE Select
- NM_001372044
- Type
- Deletion
- Location
- chr22:50720812 (GRCh38)
- Gene constraint
- LOEUF 0.446 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 53.36 · 3 PDB
- Residue 1069
- the 'disordered' region
Similar variants
- SHANK3 c.3904del Pathogenic/Likely pathogenic ★★ same condition
- SHANK3 p.Arg1330fs Pathogenic ★★ same condition
- SHANK3 p.Gln1318fs Pathogenic ★★ same condition
- SHANK3 p.Leu1217fs Pathogenic/Likely pathogenic ★★ same condition
- SHANK3 p.Val1432fs Pathogenic ★★ same condition
- SHANK3 c.2324+1del Likely pathogenic ★ same condition
- SHANK3 p.Ala1076fs Pathogenic ★ same condition
- SHANK3 p.Ala1195fs 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/shank3-p-pro1069fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown