SHANK2 p.Pro76=
c.228G>A · VCV4873756
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0524%, sas)
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 -12 | GERP -4.6 |
| Overall | ||
| CADD | 0.86 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0524%
South Asian · 44/84,046 alleles
Filtering AF
0.0401%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0357%
Overall
0.00503%
78/1,551,664 alleles · ultra-rare
exomes 73/1,399,346 · genomes 5/152,318 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0524% | 1,910 |
| Remaining individualsnot grpmax-eligible | 0.00832% | 12,023 |
| Admixed American | 0.00392% | 25,505 |
| European (non-Finnish) | 0.00235% | 42,480 |
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.Pro76=
- Coding
- c.228G>A
- MANE Select
- NM_012309
- Type
- single nucleotide variant
- Location
- chr11:71119012 (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.Pro76Leu Conflicting classifications of pathogenicity ★ same residue
- 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
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-pro76 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown