Is PTCH2 p.Leu855= (c.2565C>T) pathogenic?

PTCH2 p.Leu855= (c.2565C>T) is classified Benign in PTCH2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-28). Low-frequency (popmax 4.72%, amr); Associated with basal cell carcinoma, susceptibility to, 1.

What condition is associated with PTCH2 p.Leu855= (c.2565C>T)?

PTCH2 p.Leu855= (c.2565C>T) is associated with basal cell carcinoma, susceptibility to, 1, nevoid basal cell carcinoma syndrome, medulloblastoma (ClinVar).

How common is PTCH2 p.Leu855= (c.2565C>T) in the general population?

PTCH2 p.Leu855= (c.2565C>T) is low-frequency (popmax 4.72%, amr) (gnomAD).

PTCH2 p.Leu855=

c.2565C>T · rs34245589 · VCV239558

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.72%, amr)

Conditions

basal cell carcinoma, susceptibility to, 1

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 1.8	GERP -1.6, phastCons 1
Overall
CADD	3.439	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.72% Admixed American · 2,833/60,022 alleles

Filtering AF 4.58% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.52%

Overall 0.191% 3,091/1,614,126 alleles · low-frequency exomes 2,457/1,461,800 · genomes 634/152,326 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	4.72%	21
Remaining individualsnot grpmax-eligible	0.211%	474
African / African-American	0.0919%	1,088
European (non-Finnish)	0.00475%	21,072
East Asian	0.00223%	44,882

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.Leu855=
Coding: c.2565C>T
MANE Select: NM_003738
dbSNP: rs34245589
Type: single nucleotide variant
Location: chr1:44827032 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25
Residue 855: 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: nevoid basal cell carcinoma syndrome medulloblastoma

Similar variants

PTCH2 p.Leu855Phe Uncertain significance ★★ ⚠ same residue
PTCH2 c.2976+2T>C Uncertain significance ★★ same condition
PTCH2 c.526-2A>G Uncertain significance ★★ same condition
PTCH2 c.617+4A>T 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

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-leu855 (accessed [today's date]).

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