SHANK3 p.Ala490=
c.1470C>T · rs116756129 · VCV588015
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.39%, 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 -5.8 | GERP -4.4 |
| Overall | ||
| CADD | 0.42 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.39%
African / African-American · 1,037/74,376 alleles
Filtering AF
1.32%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.3%
Overall
0.1%
1,591/1,586,280 alleles · low-frequency
exomes 956/1,434,152 · genomes 635/152,128 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.39% | 72 |
| Ashkenazi Jewishnot grpmax-eligible | 0.254% | 393 |
| Admixed American | 0.22% | 455 |
| Middle Eastern | 0.182% | 548 |
| Remaining individualsnot grpmax-eligible | 0.174% | 575 |
| European (non-Finnish) | 0.0197% | 5,075 |
| South Asian | 0.00923% | 10,834 |
| East Asian | 0.0023% | 43,486 |
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.Ala490=
- Coding
- c.1470C>T
- MANE Select
- NM_001372044
- dbSNP
- rs116756129
- Type
- single nucleotide variant
- Location
- chr22:50694989 (GRCh38)
- Gene constraint
- LOEUF 0.446 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 53.36 · 3 PDB
- Residue 490
- the 'disordered' region
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-ala490 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown