Is PTCH2 p.Pro773fs (c.2315dup) pathogenic?

PTCH2 p.Pro773fs (c.2315dup) is classified Conflicting classifications of pathogenicity in PTCH2 (ClinVar, Conflicting submitters, 1 submitter; last evaluated 2026-08-03). Ultra-rare (popmax 0.033%, mid); Associated with basal cell carcinoma, susceptibility to, 1.

What condition is associated with PTCH2 p.Pro773fs (c.2315dup)?

PTCH2 p.Pro773fs (c.2315dup) is associated with basal cell carcinoma, susceptibility to, 1, hereditary breast carcinoma (ClinVar).

How common is PTCH2 p.Pro773fs (c.2315dup) in the general population?

PTCH2 p.Pro773fs (c.2315dup) is ultra-rare (popmax 0.033%, mid) (gnomAD).

PTCH2 p.Pro773fs

c.2315dup · rs771498368 · VCV2573189

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Conditions

basal cell carcinoma, susceptibility to, 1

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 15 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -9.9	GERP -3.8

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,054 alleles

Filtering AF 0.00583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.00031% 5/1,613,858 alleles · ultra-rare exomes 5/1,461,800 · genomes 0/152,058 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,027
South Asian	0.0022%	45,539
Remaining individualsnot grpmax-eligible	0.0016%	62,504

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.Pro773fs
Coding: c.2315dup
MANE Select: NM_003738
dbSNP: rs771498368
Type: Duplication
Location: chr1:44827457 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25
Residue 773: the 'extracellular domain 2 (ecd2)' region

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

Disease context

basal cell carcinoma, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast carcinoma

Similar variants

PTCH2 p.Pro773Leu Uncertain significance ★★ ⚠ same residue
PTCH2 p.Pro773Thr Uncertain significance ★ ⚠ same residue
PTCH2 p.Pro773= Likely benign ★ same residue
PTCH2 c.617+4A>T Uncertain significance ★★ same condition
PTCH2 p.Ala1090Val Uncertain significance ★★ ⚠ same condition
PTCH2 p.Ala371Gly Uncertain significance ★★ ⚠ same condition
PTCH2 p.Ala419Thr Uncertain significance ★★ ⚠ same condition
PTCH2 p.Ala755Pro 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-pro773fs (accessed [today's date]).

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