SHANK3 p.Arg136Pro
c.407G>C · VCV3795527
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.72e-05%, nfe)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.206 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 6.1 | GERP -4.3, phastCons 1 |
| Overall | ||
| CADD | 18.95 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.72e-05%
European (non-Finnish) · 1/1,146,856 alleles
Overall
6.46e-05%
1/1,547,956 alleles · very rare
exomes 1/1,395,704 · genomes 0/152,252 · joint denominator
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.Arg136Pro
- Coding
- c.407G>C
- MANE Select
- NM_001372044
- Type
- single nucleotide variant
- Location
- chr22:50675166 (GRCh38)
- Gene constraint
- LOEUF 0.446 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 53.36 · 3 PDB
- Residue 136
- the 'intramolecular interaction with the ank repeats' 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-arg136pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown