SHANK3 p.Pro889=
c.2667G>C · rs1569114747 · VCV587929
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.016%, sas)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.33 | GERP -2.7, phastCons 0.009 |
| Overall | ||
| CADD | 8.533 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.016%
South Asian · 12/75,116 alleles
Filtering AF
0.00919%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0072%
Overall
0.00141%
20/1,413,668 alleles · ultra-rare
exomes 20/1,266,232 · genomes 0/147,436 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.016% | 6,260 |
| European (non-Finnish) | 0.000747% | 133,833 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- SHANK3
- Protein
- p.Pro889=
- Coding
- c.2667G>C
- MANE Select
- NM_001372044
- dbSNP
- rs1569114747
- Type
- single nucleotide variant
- Location
- chr22:50720275 (GRCh38)
- Gene constraint
- LOEUF 0.446 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 53.36 · 3 PDB
- Residue 889
- the 'disordered' region
Similar variants
- SHANK3 p.Arg166Ter Pathogenic/Likely pathogenic ★★ same condition
- SHANK3 p.Gln1543Ter Pathogenic/Likely pathogenic ★★ same condition
- SHANK3 c.2279G>A Uncertain significance ★★ same condition
- SHANK3 p.Ala901Thr Uncertain significance ★★ same condition
- SHANK3 p.Arg1298Ser Uncertain significance ★★ same condition
- SHANK3 p.Arg1537Cys Uncertain significance ★★ same condition
- SHANK3 p.Arg380Cys Uncertain significance ★★ same condition
- SHANK3 p.Arg430Gln 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-pro889 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown