SHANK3 p.Ala207=
c.621A>C · VCV3898184
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, mid)
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 0.005 | GERP -1.1, phastCons 0.76 |
| Overall | ||
| CADD | 9.687 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
Middle Eastern · 3/6,060 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00718%
Overall
0.00062%
10/1,613,364 alleles · ultra-rare
exomes 10/1,461,026 · genomes 0/152,338 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0495% | 2,020 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,823 |
| South Asian | 0.00329% | 30,359 |
| African / African-American | 0.00133% | 75,058 |
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.Ala207=
- Coding
- c.621A>C
- MANE Select
- NM_001372044
- Type
- single nucleotide variant
- Location
- chr22:50678641 (GRCh38)
- Gene constraint
- LOEUF 0.446 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 53.36 · 3 PDB
Similar variants
- SHANK3 c.2455+1G>A Pathogenic ★★ same type
- SHANK3 c.2455+1G>C Pathogenic/Likely pathogenic ★★ same type
- SHANK3 c.2838C>G Pathogenic ★★ same type
- SHANK3 p.Arg166Ter Pathogenic/Likely pathogenic ★★ same type
- SHANK3 p.Arg1733Ter Pathogenic/Likely pathogenic ★★ same type
- SHANK3 p.Arg432Ter Pathogenic ★★ same type
- SHANK3 p.Asp1564Tyr Pathogenic ★★ same type
- SHANK3 p.Gln1364Ter Pathogenic ★★ 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/shank3-p-ala207 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown