SHANK2 p.Pro194=
c.582G>A · rs374802574 · VCV3045460
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.82%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.3 | GERP -4.8, phastCons 0.9 |
| Overall | ||
| CADD | 7.075 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.82%
South Asian · 689/84,030 alleles
Filtering AF
0.769%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.749%
Overall
0.0486%
754/1,550,726 alleles · rare
exomes 706/1,398,426 · genomes 48/152,300 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.82% | 122 |
| Remaining individualsnot grpmax-eligible | 0.0566% | 1,767 |
| African / African-American | 0.015% | 6,649 |
| Admixed American | 0.0118% | 8,501 |
| East Asian | 0.00489% | 20,452 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00349% | 28,648 |
| European (non-Finnish) | 0.00096% | 104,194 |
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.Pro194=
- Coding
- c.582G>A
- MANE Select
- NM_012309
- dbSNP
- rs374802574
- Type
- single nucleotide variant
- Location
- chr11:71109951 (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.Pro194Leu 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-pro194 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown