Is PTCH2 p.Leu64= (c.190T>C) pathogenic?

PTCH2 p.Leu64= (c.190T>C) is classified Benign/Likely benign in PTCH2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-23). Rare (popmax 0.187%, sas); Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with PTCH2 p.Leu64= (c.190T>C)?

PTCH2 p.Leu64= (c.190T>C) is associated with nevoid basal cell carcinoma syndrome (ClinVar).

How common is PTCH2 p.Leu64= (c.190T>C) in the general population?

PTCH2 p.Leu64= (c.190T>C) is rare (popmax 0.187%, sas) (gnomAD).

PTCH2 p.Leu64=

c.190T>C · rs199655603 · VCV415454

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.187%, sas)

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 -0.22	GERP -3.5
Overall
CADD	2.135	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.187% South Asian · 170/91,090 alleles

Filtering AF 0.164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.155%

Overall 0.0161% 260/1,614,246 alleles · rare exomes 237/1,461,892 · genomes 23/152,354 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.187%	536
Ashkenazi Jewishnot grpmax-eligible	0.179%	559
Remaining individualsnot grpmax-eligible	0.0224%	4,465
European (non-Finnish)	0.00195%	51,306

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.Leu64=
Coding: c.190T>C
MANE Select: NM_003738
dbSNP: rs199655603
Type: single nucleotide variant
Location: chr1:44841922 (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-leu64 (accessed [today's date]).

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