SHH p.Arg302=
c.906G>A · VCV4898695
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00736%, afr)
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 -1.1 | GERP -3, phastCons 0.001 |
| Overall | ||
| CADD | 2.803 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00736%
African / African-American · 5/67,968 alleles
Filtering AF
0.00285%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00186%
Overall
0.000471%
7/1,485,876 alleles · very rare
exomes 3/1,333,958 · genomes 4/151,918 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00736% | 13,594 |
| Remaining individualsnot grpmax-eligible | 0.00173% | 57,658 |
| European (non-Finnish) | 8.86e-05% | 1,128,641 |
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.Arg302=
- Coding
- c.906G>A
- MANE Select
- NM_000193
- Type
- single nucleotide variant
- Location
- chr7:155803383 (GRCh38)
- Gene constraint
- LOEUF 0.493 · pLI 0.98 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.23 · 20 PDB
- Residue 302
- the 'disordered' region
Similar variants
- SHH p.Arg302Gln Uncertain significance ★ ⚠ 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
- SHH p.Leu271Pro 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-arg302 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown