Is PTCH2 p.Val502= (c.1506C>G) pathogenic?

PTCH2 p.Val502= (c.1506C>G) is classified Benign/Likely benign in PTCH2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-01). Rare (popmax 0.229%, afr); Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with PTCH2 p.Val502= (c.1506C>G)?

PTCH2 p.Val502= (c.1506C>G) is associated with nevoid basal cell carcinoma syndrome (ClinVar).

How common is PTCH2 p.Val502= (c.1506C>G) in the general population?

PTCH2 p.Val502= (c.1506C>G) is rare (popmax 0.229%, afr) (gnomAD).

PTCH2 p.Val502=

c.1506C>G · rs11573582 · VCV695910

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.229%, afr)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6.1	GERP -4.1
Overall
CADD	0.024	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.229% African / African-American · 172/75,048 alleles

Filtering AF 0.201% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.191%

Overall 0.0118% 190/1,613,858 alleles · rare exomes 84/1,461,514 · genomes 106/152,344 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.229%	436
Middle Eastern	0.0167%	6,006
Admixed American	0.015%	6,665
Remaining individualsnot grpmax-eligible	0.0112%	8,927
European (non-Finnish)	8.48e-05%	1,179,906

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.Val502=
Coding: c.1506C>G
MANE Select: NM_003738
dbSNP: rs11573582
Type: single nucleotide variant
Location: chr1:44828590 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25
Residue 502: the ssd domain

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-val502 (accessed [today's date]).

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