SHANK2 p.Pro447=
c.1341C>T · rs202196892 · VCV2642094
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.79%, mid)
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 -2 | GERP -3.3 |
| Overall | ||
| CADD | 2.094 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.79%
Middle Eastern · 78/4,358 alleles
Filtering AF
1.47%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.35%
Overall
0.164%
1,175/717,126 alleles · low-frequency
exomes 979/564,750 · genomes 196/152,376 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 1.79% | 56 |
| Ashkenazi Jewishnot grpmax-eligible | 0.737% | 136 |
| Remaining individualsnot grpmax-eligible | 0.269% | 372 |
| South Asian | 0.265% | 378 |
| Admixed American | 0.168% | 595 |
| European (non-Finnish) | 0.143% | 700 |
| African / African-American | 0.0349% | 2,869 |
| Finnishnot grpmax-eligible | 0.00512% | 19,525 |
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
- SHANK2
- Protein
- p.Pro447=
- Coding
- c.1341C>T
- MANE Select
- NM_012309
- dbSNP
- rs202196892
- Type
- single nucleotide variant
- Location
- chr11:70820516 (GRCh38)
- Gene constraint
- LOEUF 0.417 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 52.58 · 2 PDB
Similar variants
- SHANK2 c.2439+1G>A Pathogenic/Likely pathogenic ★★ same type
- SHANK2 p.Arg185Ter Pathogenic ★★ same type
- SHANK2 p.Arg642Ter Pathogenic ★★ same type
- SHANK2 p.Arg841Ter Pathogenic ★★ same type
- SHANK2 p.Gln663Ter Likely pathogenic ★★ same type
- SHANK2 p.Glu252Ter Likely pathogenic ★★ same type
- SHANK2 p.Ala1729Thr Uncertain significance ★★ ⚠ same type
- SHANK2 p.Arg1089His Uncertain significance ★★ 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/shank2-p-pro447 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown