SHANK2 p.Pro44=
c.132G>A · rs781962815 · VCV3031189
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00785%, amr)
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 -13 | GERP -3.8 |
| Overall | ||
| CADD | 0.902 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00785%
Admixed American · 4/50,970 alleles
Filtering AF
0.00263%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00153%
Overall
0.00213%
33/1,550,606 alleles · very rare
exomes 31/1,398,488 · genomes 2/152,118 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00785% | 12,743 |
| East Asian | 0.00733% | 13,642 |
| European (non-Finnish) | 0.00218% | 45,878 |
| South Asian | 0.00119% | 84,048 |
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.Pro44=
- Coding
- c.132G>A
- MANE Select
- NM_012309
- dbSNP
- rs781962815
- Type
- single nucleotide variant
- Location
- chr11:71147195 (GRCh38)
- Gene constraint
- LOEUF 0.417 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 52.58 · 2 PDB
Similar variants
- SHANK2 p.Pro44Leu Uncertain significance ★★ same residue
- SHANK2 p.Arg227Cys Uncertain significance ★★ same condition
- SHANK2 p.Arg783His Uncertain significance ★★ ⚠ same condition
- SHANK2 p.Glu1183Lys Uncertain significance ★★ ⚠ same condition
- SHANK2 p.Pro1446Leu Uncertain significance ★★ ⚠ same condition
- SHANK2 p.Ser884Phe Uncertain significance ★★ same condition
- SHANK2 p.Arg111His Likely benign ★★ same condition
- SHANK2 p.Ile1361= Likely benign ★★ 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/shank2-p-pro44 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown