SHANK1 p.Pro48=
c.144T>C · rs1236210039 · VCV752685
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00171%, amr)
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 2.8 | GERP 1.5, phastCons 1 |
| Overall | ||
| CADD | 11.93 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00171%
Admixed American · 1/58,458 alleles
Overall
0.000124%
2/1,607,634 alleles · very rare
exomes 2/1,455,384 · genomes 0/152,250 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00171% | 58,458 |
| European (non-Finnish) | 8.49e-05% | 1,177,164 |
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
- SHANK1
- Protein
- p.Pro48=
- Coding
- c.144T>C
- MANE Select
- NM_016148
- dbSNP
- rs1236210039
- Type
- single nucleotide variant
- Location
- chr19:50716776 (GRCh38)
- Gene constraint
- LOEUF 0.383 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 48.59 · 7 PDB
- Residue 48
- the 'disordered' region
Similar variants
- SHANK1 p.Arg1048Ter Pathogenic/Likely pathogenic ★★ same type
- SHANK1 p.Arg713Ter Pathogenic ★★ same type
- SHANK1 p.Arg717Ter Pathogenic/Likely pathogenic ★★ same type
- SHANK1 p.Ala893Val Uncertain significance ★★ ⚠ same type
- SHANK1 p.Arg1423Gly Uncertain significance ★★ ⚠ same type
- SHANK1 p.Arg2153Gln Uncertain significance ★★ ⚠ same type
- SHANK1 p.Arg89His Uncertain significance ★★ ⚠ same type
- SHANK1 p.Asn1497His 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/shank1-p-pro48 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown