PTCH1 p.Pro252=
c.756T>A · rs2118428399 · VCV1545332
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0022%, sas)
Conditions
2
nevoid basal cell carcinoma syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.016 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 2.9 | GERP -0.4, phastCons 1 |
| Overall | ||
| CADD | 9.654 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0022%
South Asian · 2/91,014 alleles
Filtering AF
0.000365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000137%
Overall
0.000124%
2/1,613,590 alleles · very rare
exomes 2/1,461,588 · genomes 0/152,002 · joint denominator
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
- PTCH1
- Protein
- p.Pro252=
- Coding
- c.756T>A
- MANE Select
- NM_000264
- dbSNP
- rs2118428399
- Type
- single nucleotide variant
- Location
- chr9:95480579 (GRCh38)
- Gene constraint
- LOEUF 0.146 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 74.36 · 16 PDB
- Residue 252
- a β-strand; the 'extracellular domain 1 (ecd1)' region
Similar variants
- PTCH1 p.Pro252Arg Uncertain significance ★★ ⚠ same residue
- PTCH1 p.Pro252Ser Uncertain significance ★ ⚠ same residue
- PTCH1 p.Pro252Thr Uncertain significance ★ ⚠ same residue
- PTCH1 c.1068-1G>A Pathogenic/Likely pathogenic ★★ same condition
- PTCH1 c.1068-1G>T Likely pathogenic ★★ same condition
- PTCH1 c.1216-1G>A Pathogenic/Likely pathogenic ★★ same condition
- PTCH1 c.1347+1G>C Likely pathogenic ★★ same condition
- PTCH1 c.1348-1G>A 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/ptch1-p-pro252 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown