Is PTCH1 p.Arg294= (c.882C>A) pathogenic?

PTCH1 p.Arg294= (c.882C>A) is classified Likely benign in PTCH1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-05-14). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with PTCH1 p.Arg294= (c.882C>A)?

PTCH1 p.Arg294= (c.882C>A) is associated with hereditary neoplastic syndrome, nevoid basal cell carcinoma syndrome (ClinVar).

How common is PTCH1 p.Arg294= (c.882C>A) in the general population?

PTCH1 p.Arg294= (c.882C>A) is absent from gnomAD v4.1 (gnomAD).

PTCH1 p.Arg294=

c.882C>A · rs145893445 · VCV1641055

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic 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 -1.6	GERP -3.8
Overall
CADD	2.943	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PTCH1
Protein: p.Arg294=
Coding: c.882C>A
MANE Select: NM_000264
dbSNP: rs145893445
Type: single nucleotide variant
Location: chr9:95480453 (GRCh38)
Gene constraint: LOEUF 0.146 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 74.36 · 16 PDB
Residue 294: the 'extracellular domain 1 (ecd1)' region

Full PTCH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: nevoid basal cell carcinoma syndrome

Similar variants

PTCH1 p.Arg294Cys Uncertain significance ★ ⚠ same residue
PTCH1 p.Arg294His Conflicting classifications of pathogenicity ★ ⚠ same residue
PTCH1 p.Arg294Pro Likely benign ★ same residue
PTCH1 p.Arg294fs Pathogenic ★ same residue
PTCH1 c.1068-1G>A Pathogenic/Likely pathogenic ★★ same condition
PTCH1 c.1068-1G>T Likely pathogenic ★★ same condition
PTCH1 c.1216-1G>A Pathogenic/Likely pathogenic ★★ same condition
PTCH1 c.1347+1G>C Likely pathogenic ★★ 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/ptch1-p-arg294 (accessed [today's date]).

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