Is PTCH2 p.Pro882fs (c.2642dup) pathogenic?

PTCH2 p.Pro882fs (c.2642dup) is classified Uncertain significance in PTCH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-01). Ultra-rare (gnomAD MAF 2.141e-06); Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with PTCH2 p.Pro882fs (c.2642dup)?

PTCH2 p.Pro882fs (c.2642dup) is associated with nevoid basal cell carcinoma syndrome (ClinVar).

How common is PTCH2 p.Pro882fs (c.2642dup) in the general population?

PTCH2 p.Pro882fs (c.2642dup) is ultra-rare (gnomAD MAF 2.141e-06) (gnomAD).

PTCH2 p.Pro882fs

c.2642dup · rs1337855606 · VCV942904

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 2.141e-06)

Conditions

nevoid basal cell carcinoma syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 17 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.5	GERP -3.8

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

Global frequency 0.000214% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: PTCH2
Protein: p.Pro882fs
Coding: c.2642dup
MANE Select: NM_003738
dbSNP: rs1337855606
Type: Duplication
Location: chr1:44826954 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25
Residue 882: the 'extracellular domain 2 (ecd2)' 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.Pro882Ser Uncertain significance ★★ ⚠ same residue
PTCH2 p.Pro882= Likely benign ★ same residue
PTCH2 c.1685_1709+14dup Uncertain significance ★ same condition
PTCH2 p.Ala131fs Uncertain significance ★ same condition
PTCH2 p.Asn509fs Uncertain significance ★ same condition
PTCH2 p.Gln271fs Uncertain significance ★ same condition
PTCH2 p.Leu221fs Uncertain significance ★ same condition
PTCH2 p.Leu524fs 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-pro882fs (accessed [today's date]).

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