SHANK2 p.Asp112=
c.336C>T · rs76014490 · VCV305922
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 9.9%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.23 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.1 | GERP -4.6 |
| Overall | ||
| CADD | 2.248 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
9.9%
African / African-American · 7,243/73,146 alleles
Filtering AF
9.71%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9.63%
Overall
0.622%
9,648/1,551,716 alleles · common
exomes 5,195/1,399,418 · genomes 4,453/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 9.9% | 10 |
| East Asian | 2.87% | 35 |
| Remaining individualsnot grpmax-eligible | 0.956% | 105 |
| Admixed American | 0.837% | 119 |
| Middle Eastern | 0.467% | 214 |
| South Asian | 0.0393% | 2,547 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0314% | 3,184 |
| European (non-Finnish) | 0.0137% | 7,306 |
| Finnishnot grpmax-eligible | 0.00334% | 29,952 |
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.Asp112=
- Coding
- c.336C>T
- MANE Select
- NM_012309
- dbSNP
- rs76014490
- Type
- single nucleotide variant
- Location
- chr11:71118904 (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.Asp112Asn Uncertain significance ★ 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-asp112 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown