Is PTCH2 p.Pro182= (c.546G>A) pathogenic?

PTCH2 p.Pro182= (c.546G>A) is classified Likely benign in PTCH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-16). Ultra-rare (popmax 0.0101%, sas); Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with PTCH2 p.Pro182= (c.546G>A)?

PTCH2 p.Pro182= (c.546G>A) is associated with nevoid basal cell carcinoma syndrome (ClinVar).

How common is PTCH2 p.Pro182= (c.546G>A) in the general population?

PTCH2 p.Pro182= (c.546G>A) is ultra-rare (popmax 0.0101%, sas) (gnomAD).

PTCH2 p.Pro182=

c.546G>A · rs547735253 · VCV703895

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0101%, sas)

Conditions

nevoid basal cell carcinoma syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -12	GERP -3.5
Overall
CADD	0.125	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0101% South Asian · 9/89,480 alleles

Filtering AF 0.00522% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00391%

Overall 0.00125% 20/1,599,904 alleles · ultra-rare exomes 19/1,447,806 · genomes 1/152,098 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0101%	9,942
Admixed American	0.0035%	28,570
Ashkenazi Jewishnot grpmax-eligible	0.00342%	29,282
Remaining individualsnot grpmax-eligible	0.00161%	61,974
African / African-American	0.00134%	74,492
European (non-Finnish)	0.000511%	195,532

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: PTCH2
Protein: p.Pro182=
Coding: c.546G>A
MANE Select: NM_003738
dbSNP: rs547735253
Type: single nucleotide variant
Location: chr1:44831777 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25
Residue 182: the 'extracellular domain 1 (ecd1)' region

Full PTCH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nevoid basal cell carcinoma syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PTCH2 p.Pro182Leu Uncertain significance ★ ⚠ same residue
PTCH2 c.2976+2T>C Uncertain significance ★★ same condition
PTCH2 c.526-2A>G Uncertain significance ★★ same condition
PTCH2 c.618-6C>A Uncertain significance ★★ same condition
PTCH2 p.Ala1052Thr Uncertain significance ★★ ⚠ same condition
PTCH2 p.Ala1090Val Uncertain significance ★★ ⚠ same condition
PTCH2 p.Ala203Val Uncertain significance ★★ same condition
PTCH2 p.Ala21Thr Uncertain significance ★★ ⚠ 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/ptch2-p-pro182 (accessed [today's date]).

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