SHH p.Pro41fs
c.121_122del · VCV3775159
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
holoprosencephaly 3
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 1 of 3 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 0.53 | GERP -3.3, phastCons 0.87 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- SHH
- Protein
- p.Pro41fs
- Coding
- c.121_122del
- MANE Select
- NM_000193
- Type
- Deletion
- Location
- chr7:155812001 (GRCh38)
- Gene constraint
- LOEUF 0.493 · pLI 0.98 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.23 · 20 PDB
- Residue 41
- an α-helix
Similar variants
- SHH p.Pro41Ala Uncertain significance ★ ⚠ same residue
- SHH p.Thr429fs Pathogenic ★★ same condition
- SHH c.-3226_301-2327del Likely pathogenic ★ same condition
- SHH p.Ala391fs Pathogenic ★ same condition
- SHH p.Arg244fs Pathogenic ★ same condition
- SHH p.Arg34fs Pathogenic ★ same condition
- SHH p.Gln437fs Pathogenic ★ same condition
- SHH p.Glu284fs 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-pro41fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown