SHANK3 p.Arg883Pro
c.2648G>C · rs2083272071 · VCV995856
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Phelan-McDermid syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.18 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 9.3 | GERP 0.34, phastCons 1 |
| Overall | ||
| CADD | 24.2 | PHRED · no single calibrated threshold — expert panels disagree |
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
- SHANK3
- Protein
- p.Arg883Pro
- Coding
- c.2648G>C
- MANE Select
- NM_001372044
- dbSNP
- rs2083272071
- Type
- single nucleotide variant
- Location
- chr22:50720256 (GRCh38)
- Gene constraint
- LOEUF 0.446 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 53.36 · 3 PDB
- Residue 883
- the 'disordered' region
Similar variants
- SHANK3 c.2455+1G>A Pathogenic ★★ same condition
- SHANK3 c.2838C>G Pathogenic ★★ same condition
- SHANK3 p.Arg166Ter Pathogenic/Likely pathogenic ★★ same condition
- SHANK3 p.Arg432Ter Pathogenic ★★ same condition
- SHANK3 p.Asp1564Tyr Pathogenic ★★ same condition
- SHANK3 p.Gln1364Ter Pathogenic ★★ same condition
- SHANK3 p.Gln1737Ter Pathogenic/Likely pathogenic ★★ same condition
- SHANK3 c.1235C>G Uncertain significance ★★ 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-arg883pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown