Is PTCH2 p.Arg397= (c.1191T>A) pathogenic?

PTCH2 p.Arg397= (c.1191T>A) is classified Likely benign in PTCH2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-04-09). Very rare (popmax 0.00153%, nfe); Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with PTCH2 p.Arg397= (c.1191T>A)?

PTCH2 p.Arg397= (c.1191T>A) is associated with nevoid basal cell carcinoma syndrome (ClinVar).

How common is PTCH2 p.Arg397= (c.1191T>A) in the general population?

PTCH2 p.Arg397= (c.1191T>A) is very rare (popmax 0.00153%, nfe) (gnomAD).

PTCH2 p.Arg397=

c.1191T>A · rs201286252 · VCV2781209

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

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	all four deltas below 0.2 · A>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2	GERP -3.8
Overall
CADD	1.273	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00153% European (non-Finnish) · 18/1,180,034 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00112% 18/1,614,224 alleles · very rare exomes 17/1,461,880 · genomes 1/152,344 · joint denominator

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.Arg397=
Coding: c.1191T>A
MANE Select: NM_003738
dbSNP: rs201286252
Type: single nucleotide variant
Location: chr1:44829426 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25
Residue 397: 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 p.Arg397Cys Uncertain significance ★ ⚠ same residue
PTCH2 p.Arg397Gly Uncertain significance ★ ⚠ same residue
PTCH2 p.Arg397fs 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

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-arg397 (accessed [today's date]).

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