SHANK2 p.Pro1432=
c.4296G>A · rs559537625 · VCV436714
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, eas)
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 -2.5 | GERP -4.5 |
| Overall | ||
| CADD | 4.635 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
East Asian · 6/44,892 alleles
Filtering AF
0.0111%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0105%
Overall
0.0107%
172/1,613,884 alleles · ultra-rare
exomes 161/1,461,840 · genomes 11/152,044 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0134% | 7,482 |
| European (non-Finnish) | 0.0128% | 7,815 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,927 |
| Admixed American | 0.005% | 19,999 |
| African / African-American | 0.00267% | 37,428 |
| South Asian | 0.0022% | 45,533 |
| Finnishnot grpmax-eligible | 0.00156% | 63,968 |
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.Pro1432=
- Coding
- c.4296G>A
- MANE Select
- NM_012309
- dbSNP
- rs559537625
- Type
- single nucleotide variant
- Location
- chr11:70485997 (GRCh38)
- Gene constraint
- LOEUF 0.417 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 52.58 · 2 PDB
- Residue 1432
- the 'disordered' region
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-pro1432 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown