Is PTCH2 p.Pro16= (c.48C>T) pathogenic?

PTCH2 p.Pro16= (c.48C>T) is classified Likely benign in PTCH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). Very rare (popmax 0.00979%, eas); Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with PTCH2 p.Pro16= (c.48C>T)?

PTCH2 p.Pro16= (c.48C>T) is associated with nevoid basal cell carcinoma syndrome (ClinVar).

How common is PTCH2 p.Pro16= (c.48C>T) in the general population?

PTCH2 p.Pro16= (c.48C>T) is very rare (popmax 0.00979%, eas) (gnomAD).

PTCH2 p.Pro16=

c.48C>T · rs1241582640 · VCV753860

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00979%, eas)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -1.8, phastCons 1
Overall
CADD	6.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00979% East Asian · 4/40,874 alleles

Filtering AF 0.00328% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00194%

Overall 0.000258% 4/1,550,854 alleles · very rare exomes 2/1,398,636 · genomes 2/152,218 · joint denominator

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.Pro16=
Coding: c.48C>T
MANE Select: NM_003738
dbSNP: rs1241582640
Type: single nucleotide variant
Location: chr1:44842885 (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

Similar variants

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
PTCH2 p.Ala371Gly 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-pro16 (accessed [today's date]).

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