Is PTCH2 p.Pro1116= (c.3348G>A) pathogenic?

PTCH2 p.Pro1116= (c.3348G>A) is classified Likely benign in PTCH2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-13). Ultra-rare (popmax 0.0184%, amr); Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with PTCH2 p.Pro1116= (c.3348G>A)?

PTCH2 p.Pro1116= (c.3348G>A) is associated with nevoid basal cell carcinoma syndrome, basal cell carcinoma, susceptibility to, 1 (ClinVar).

How common is PTCH2 p.Pro1116= (c.3348G>A) in the general population?

PTCH2 p.Pro1116= (c.3348G>A) is ultra-rare (popmax 0.0184%, amr) (gnomAD).

PTCH2 p.Pro1116=

c.3348G>A · rs576830052 · VCV453939

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0184%, amr)

Conditions

nevoid basal cell carcinoma syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.062	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.16	GERP -3.8, phastCons 0.86
Overall
CADD	3.089	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0184% Admixed American · 11/59,916 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00786%

Overall 0.00205% 33/1,613,048 alleles · ultra-rare exomes 30/1,460,848 · genomes 3/152,200 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0184%	5,447
Remaining individualsnot grpmax-eligible	0.00961%	10,406
East Asian	0.00223%	44,846
European (non-Finnish)	0.00127%	78,648

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.Pro1116=
Coding: c.3348G>A
MANE Select: NM_003738
dbSNP: rs576830052
Type: single nucleotide variant
Location: chr1:44823078 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25

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

Also linked: basal cell carcinoma, susceptibility to, 1

Similar variants

PTCH2 p.Pro1116Leu Uncertain significance ★★ same residue
PTCH2 c.2976+2T>C Uncertain significance ★★ same condition
PTCH2 c.526-2A>G Uncertain significance ★★ same condition
PTCH2 c.617+4A>T 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

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-pro1116 (accessed [today's date]).

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