SHANK2 p.Pro267=
c.801G>A · VCV4681824
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.1%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.014 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.37 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -10 | GERP -4.5 |
| Overall | ||
| CADD | 3.283 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.1%
Admixed American · 51/50,956 alleles
Filtering AF
0.0781%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0703%
Overall
0.00412%
64/1,551,564 alleles · rare
exomes 58/1,399,622 · genomes 6/151,942 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.1% | 999 |
| South Asian | 0.00595% | 16,810 |
| Remaining individualsnot grpmax-eligible | 0.00333% | 30,068 |
| East Asian | 0.00244% | 40,908 |
| African / African-American | 0.00137% | 72,930 |
| European (non-Finnish) | 0.000349% | 286,759 |
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
- SHANK2
- Protein
- p.Pro267=
- Coding
- c.801G>A
- MANE Select
- NM_012309
- Type
- single nucleotide variant
- Location
- chr11:71092533 (GRCh38)
- Gene constraint
- LOEUF 0.417 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 52.58 · 2 PDB
Similar variants
- SHANK2 c.2439+1G>A Pathogenic/Likely pathogenic ★★ same type
- SHANK2 p.Arg185Ter Pathogenic ★★ same type
- SHANK2 p.Arg642Ter Pathogenic ★★ same type
- SHANK2 p.Arg841Ter Pathogenic ★★ same type
- SHANK2 p.Gln663Ter Likely pathogenic ★★ same type
- SHANK2 p.Glu252Ter Likely pathogenic ★★ same type
- SHANK2 p.Ala1729Thr Uncertain significance ★★ ⚠ same type
- SHANK2 p.Arg1089His Uncertain significance ★★ 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/shank2-p-pro267 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown