Is PTCH2 p.Pro129= (c.387C>G) pathogenic?

PTCH2 p.Pro129= (c.387C>G) is classified Likely benign in PTCH2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-15). Very rare (popmax 0.00223%, eas); Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with PTCH2 p.Pro129= (c.387C>G)?

PTCH2 p.Pro129= (c.387C>G) is associated with nevoid basal cell carcinoma syndrome (ClinVar).

How common is PTCH2 p.Pro129= (c.387C>G) in the general population?

PTCH2 p.Pro129= (c.387C>G) is very rare (popmax 0.00223%, eas) (gnomAD).

PTCH2 p.Pro129=

c.387C>G · rs772262804 · VCV2021796

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, 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 -13	GERP -4.1
Overall
CADD	0.016	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,876 alleles

Overall 0.000124% 2/1,614,148 alleles · very rare exomes 2/1,461,894 · genomes 0/152,254 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,876
European (non-Finnish)	8.47e-05%	1,180,032

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.Pro129=
Coding: c.387C>G
MANE Select: NM_003738
dbSNP: rs772262804
Type: single nucleotide variant
Location: chr1:44832220 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25
Residue 129: 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.Pro129Leu 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-pro129 (accessed [today's date]).

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