Is PTCH2 p.Asp829= (c.2487C>T) pathogenic?

PTCH2 p.Asp829= (c.2487C>T) is classified Benign in PTCH2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 22.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with PTCH2 p.Asp829= (c.2487C>T)?

PTCH2 p.Asp829= (c.2487C>T) is associated with nevoid basal cell carcinoma syndrome (ClinVar).

PTCH2 p.Asp829=

Q: How common is PTCH2 p.Asp829= (c.2487C>T) in the general population?

PTCH2 p.Asp829= (c.2487C>T) is common (popmax 22.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2487C>T · rs2295996 · VCV1166504

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 22.9%, eas) — too common for a highly-penetrant pathogenic allele

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 -1.4	GERP -4.1
Overall
CADD	0.987	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 22.9% East Asian · 10,252/44,858 alleles

Filtering AF 22.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 22.3%

Overall 16.4% 265,440/1,613,950 alleles · common exomes 243,558/1,461,718 · genomes 21,882/152,232 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	22.9%	4
Amishnot grpmax-eligible	22.7%	4
Admixed American	17.4%	6
European (non-Finnish)	16.9%	6
South Asian	16.1%	6
Remaining individualsnot grpmax-eligible	15.7%	6
Ashkenazi Jewishnot grpmax-eligible	15.4%	7
Finnishnot grpmax-eligible	15.1%	7
Middle Eastern	13.4%	7
African / African-American	7.93%	13

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.Asp829=
Coding: c.2487C>T
MANE Select: NM_003738
dbSNP: rs2295996
Type: single nucleotide variant
Location: chr1:44827194 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25
Residue 829: the 'extracellular domain 2 (ecd2)' 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.Asp829Glu Uncertain significance ★ ⚠ same residue
PTCH2 p.Asp829Val 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

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-asp829 (accessed [today's date]).

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