SHH p.Ser362=
c.1086G>C · rs747202947 · VCV3051037
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00218%, 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 0.18 | GERP -4.2, phastCons 0.96 |
| Overall | ||
| CADD | 7.452 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00218%
Admixed American · 1/45,886 alleles
Filtering AF
0.000839%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000679%
Overall
0.00113%
17/1,499,666 alleles · very rare
exomes 17/1,347,674 · genomes 0/151,992 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00218% | 45,886 |
| European (non-Finnish) | 0.00142% | 70,568 |
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
- SHH
- Protein
- p.Ser362=
- Coding
- c.1086G>C
- MANE Select
- NM_000193
- dbSNP
- rs747202947
- Type
- single nucleotide variant
- Location
- chr7:155803203 (GRCh38)
- Gene constraint
- LOEUF 0.493 · pLI 0.98 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.23 · 20 PDB
- Residue 362
- a UniProt-annotated variant site (in hpe3)
Similar variants
- SHH p.Ser362Leu Likely pathogenic ★ same residue
- SHH p.Ser362Ter Pathogenic ★ same residue
- SHH c.562+1G>A Pathogenic ★★ same type
- SHH p.Arg72Ter Pathogenic ★★ same type
- SHH p.Asp222Asn Likely pathogenic ★★ same type
- SHH p.Cys198Arg Pathogenic/Likely pathogenic ★★ same type
- SHH p.Cys198Ser Likely pathogenic ★★ same type
- SHH p.Leu266Phe Likely 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/shh-p-ser362 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown