SHH p.Pro293=
c.879G>A · rs911838783 · VCV762714
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0438%, mid)
Conditions
1
holoprosencephaly 3
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 0.32 | GERP -3.4, phastCons 0.065 |
| Overall | ||
| CADD | 5.251 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0438%
Middle Eastern · 2/4,568 alleles
Filtering AF
0.00777%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00411%
Overall
0.00105%
16/1,519,190 alleles · ultra-rare
exomes 16/1,367,004 · genomes 0/152,186 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0438% | 2,284 |
| African / African-American | 0.0114% | 8,810 |
| Remaining individualsnot grpmax-eligible | 0.00677% | 14,768 |
| European (non-Finnish) | 0.000175% | 570,272 |
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.Pro293=
- Coding
- c.879G>A
- MANE Select
- NM_000193
- dbSNP
- rs911838783
- Type
- single nucleotide variant
- Location
- chr7:155803410 (GRCh38)
- Gene constraint
- LOEUF 0.493 · pLI 0.98 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.23 · 20 PDB
- Residue 293
- the 'disordered' region
Similar variants
- SHH p.Pro293Arg Uncertain significance ★ ⚠ same residue
- SHH p.Arg72Ter Pathogenic ★★ same condition
- SHH p.Asp222Asn Likely pathogenic ★★ same condition
- SHH p.Leu266Phe Likely pathogenic ★★ same condition
- SHH p.Leu271Pro Likely pathogenic ★★ same condition
- SHH p.Pro347Arg Likely pathogenic ★★ same condition
- SHH p.Pro347Leu Pathogenic/Likely pathogenic ★★ same condition
- SHH p.Ser436Ter Pathogenic/Likely pathogenic ★★ 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/shh-p-pro293 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown