Is PTCH2 p.Glu607= (c.1821A>G) pathogenic?

PTCH2 p.Glu607= (c.1821A>G) is classified Benign in PTCH2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 25.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with PTCH2 p.Glu607= (c.1821A>G)?

PTCH2 p.Glu607= (c.1821A>G) is associated with nevoid basal cell carcinoma syndrome (ClinVar).

PTCH2 p.Glu607=

Q: How common is PTCH2 p.Glu607= (c.1821A>G) in the general population?

PTCH2 p.Glu607= (c.1821A>G) is common (popmax 25.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1821A>G · rs2295997 · VCV1169858

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 25.8%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.18	GERP -0.74, phastCons 0.92
Overall
CADD	5.667	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 25.8% East Asian · 11,596/44,872 alleles

Filtering AF 25.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 25.3%

Overall 18.3% 295,825/1,613,972 alleles · common exomes 266,946/1,461,782 · genomes 28,879/152,190 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	25.8%	4
Admixed American	21.8%	5
African / African-American	21.2%	5
South Asian	19.1%	5
Remaining individualsnot grpmax-eligible	18.9%	5
Finnishnot grpmax-eligible	18.8%	5
European (non-Finnish)	17.6%	6
Ashkenazi Jewishnot grpmax-eligible	16.6%	6
Middle Eastern	12.7%	8
Amishnot grpmax-eligible	10.2%	10

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.Glu607=
Coding: c.1821A>G
MANE Select: NM_003738
dbSNP: rs2295997
Type: single nucleotide variant
Location: chr1:44828080 (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-glu607 (accessed [today's date]).

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