SHANK3 p.Ala232=
c.696C>T · rs201013911 · VCV588720
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.18%, afr)
Conditions
1
Inborn genetic diseases
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 -0.49 | GERP -4.7, phastCons 0.022 |
| Overall | ||
| CADD | 7.982 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.18%
African / African-American · 135/75,056 alleles
Filtering AF
0.155%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.146%
Overall
0.00955%
154/1,613,012 alleles · rare
exomes 82/1,460,682 · genomes 72/152,330 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.18% | 556 |
| Admixed American | 0.0183% | 5,451 |
| Middle Eastern | 0.0165% | 6,058 |
| Remaining individualsnot grpmax-eligible | 0.00961% | 10,411 |
| European (non-Finnish) | 8.48e-05% | 1,179,727 |
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
- SHANK3
- Protein
- p.Ala232=
- Coding
- c.696C>T
- MANE Select
- NM_001372044
- dbSNP
- rs201013911
- Type
- single nucleotide variant
- Location
- chr22:50678791 (GRCh38)
- Gene constraint
- LOEUF 0.446 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 53.36 · 3 PDB
Similar variants
- SHANK3 p.Arg166Ter Pathogenic/Likely pathogenic ★★ same condition
- SHANK3 p.Gln1543Ter Pathogenic/Likely pathogenic ★★ same condition
- SHANK3 c.2279G>A Uncertain significance ★★ same condition
- SHANK3 p.Ala901Thr Uncertain significance ★★ same condition
- SHANK3 p.Arg1298Ser Uncertain significance ★★ same condition
- SHANK3 p.Arg1537Cys Uncertain significance ★★ same condition
- SHANK3 p.Arg380Cys Uncertain significance ★★ same condition
- SHANK3 p.Arg430Gln Uncertain significance ★★ same condition
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/shank3-p-ala232 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown