Is PTCH1 p.Val12= (c.36G>T) pathogenic?

PTCH1 p.Val12= (c.36G>T) is classified Likely benign in PTCH1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-05-01). Ultra-rare (popmax 0.0384%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with PTCH1 p.Val12= (c.36G>T)?

PTCH1 p.Val12= (c.36G>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is PTCH1 p.Val12= (c.36G>T) in the general population?

PTCH1 p.Val12= (c.36G>T) is ultra-rare (popmax 0.0384%, nfe) (gnomAD).

PTCH1 p.Val12=

c.36G>T · rs200215582 · VCV1692541

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0384%, nfe)

Conditions

hereditary neoplastic syndrome

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 5.6	GERP 1.2, phastCons 1
Overall
CADD	14.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0384% European (non-Finnish) · 453/1,179,488 alleles

Filtering AF 0.0354% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0343%

Overall 0.0301% 485/1,612,406 alleles · ultra-rare exomes 454/1,460,220 · genomes 31/152,186 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0384%	2,604
Finnishnot grpmax-eligible	0.0219%	4,567
Remaining individualsnot grpmax-eligible	0.0192%	5,201
Admixed American	0.00671%	14,903
African / African-American	0.00134%	74,846
South Asian	0.0011%	90,752

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.Val12=
Coding: c.36G>T
MANE Select: NM_000264 · reported on NM_001083603
dbSNP: rs200215582
Type: single nucleotide variant
Location: chr9:95516785 (GRCh38)
Gene constraint: LOEUF 0.146 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 74.36 · 16 PDB
Residue 12: the 'disordered' region

Full PTCH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PTCH1 p.Asp12Asn Uncertain significance ★ ⚠ same residue
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.202-2A>C Pathogenic/Likely pathogenic ★★ same condition
PTCH1 c.202-2A>G Pathogenic ★★ same condition
PTCH1 c.394+1G>A Pathogenic ★★ same condition
PTCH1 c.584+1G>A 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/ptch1-p-val12 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown