Is PTCH2 p.Ile688= (c.2064C>T) pathogenic?

PTCH2 p.Ile688= (c.2064C>T) is classified Likely benign in PTCH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-04). Ultra-rare (popmax 0.0384%, sas); Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with PTCH2 p.Ile688= (c.2064C>T)?

PTCH2 p.Ile688= (c.2064C>T) is associated with nevoid basal cell carcinoma syndrome (ClinVar).

How common is PTCH2 p.Ile688= (c.2064C>T) in the general population?

PTCH2 p.Ile688= (c.2064C>T) is ultra-rare (popmax 0.0384%, sas) (gnomAD).

PTCH2 p.Ile688=

c.2064C>T · rs755030599 · VCV524638

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0384%, 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 0.11	GERP -3.5, phastCons 0.38
Overall
CADD	2.191	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0384% South Asian · 35/91,084 alleles

Filtering AF 0.0283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0249%

Overall 0.00273% 44/1,611,140 alleles · ultra-rare exomes 44/1,458,816 · genomes 0/152,324 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0384%	2,602
Middle Eastern	0.033%	3,030
Remaining individualsnot grpmax-eligible	0.0032%	31,245
Admixed American	0.00167%	60,028
African / African-American	0.00133%	75,054
European (non-Finnish)	0.000254%	393,335

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.Ile688=
Coding: c.2064C>T
MANE Select: NM_003738
dbSNP: rs755030599
Type: single nucleotide variant
Location: chr1:44827709 (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-ile688 (accessed [today's date]).

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