SHANK3 p.Pro1124=
c.3372C>T · rs200572899 · VCV587951
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.29%, 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 -2.2 | GERP -3 |
| Overall | ||
| CADD | 5.356 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.29%
African / African-American · 967/74,934 alleles
Filtering AF
1.22%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.2%
Overall
0.0707%
1,129/1,596,328 alleles · low-frequency
exomes 565/1,444,148 · genomes 564/152,180 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.29% | 77 |
| Remaining individualsnot grpmax-eligible | 0.13% | 768 |
| Admixed American | 0.0986% | 1,014 |
| Middle Eastern | 0.0668% | 1,497 |
| South Asian | 0.0143% | 6,995 |
| European (non-Finnish) | 0.000424% | 235,649 |
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.Pro1124=
- Coding
- c.3372C>T
- MANE Select
- NM_001372044
- dbSNP
- rs200572899
- Type
- single nucleotide variant
- Location
- chr22:50720980 (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-pro1124 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown