SHANK2 p.Pro257=
c.771A>G · rs200821952 · VCV305908
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0349%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.023 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -4.5 |
| Overall | ||
| CADD | 0.282 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0349%
European (non-Finnish) · 400/1,147,042 alleles
Filtering AF
0.032%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0309%
Overall
0.0284%
440/1,551,700 alleles · ultra-rare
exomes 408/1,399,750 · genomes 32/151,950 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0349% | 2,868 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0314% | 3,184 |
| Remaining individualsnot grpmax-eligible | 0.0249% | 4,012 |
| Admixed American | 0.0118% | 8,492 |
| Finnishnot grpmax-eligible | 0.00833% | 12,010 |
| African / African-American | 0.00685% | 14,588 |
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.Pro257=
- Coding
- c.771A>G
- MANE Select
- NM_012309
- dbSNP
- rs200821952
- Type
- single nucleotide variant
- Location
- chr11:71092563 (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-pro257 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown