SHANK2 p.Ser429=
c.1287C>T · rs571788090 · VCV2642098
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0932%, 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 -0.52 | GERP -3.5 |
| Overall | ||
| CADD | 7.201 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0932%
South Asian · 63/67,566 alleles
Filtering AF
0.0747%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0681%
Overall
0.0162%
116/716,930 alleles · ultra-rare
exomes 100/564,566 · genomes 16/152,364 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0932% | 1,072 |
| Remaining individualsnot grpmax-eligible | 0.0214% | 4,680 |
| European (non-Finnish) | 0.0107% | 9,384 |
| Admixed American | 0.006% | 16,667 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00426% | 23,468 |
| African / African-American | 0.00174% | 57,384 |
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.Ser429=
- Coding
- c.1287C>T
- MANE Select
- NM_012309
- dbSNP
- rs571788090
- Type
- single nucleotide variant
- Location
- chr11:70820570 (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-ser429 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown