Is PTCH1 p.Pro568= (c.1704C>A) pathogenic?

PTCH1 p.Pro568= (c.1704C>A) is classified Likely benign in PTCH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-01). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with PTCH1 p.Pro568= (c.1704C>A)?

PTCH1 p.Pro568= (c.1704C>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is PTCH1 p.Pro568= (c.1704C>A) in the general population?

PTCH1 p.Pro568= (c.1704C>A) is absent from gnomAD v4.1 (gnomAD).

PTCH1 p.Pro568=

c.1704C>A · VCV3427340

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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 -8.4	GERP -3.8
Overall
CADD	0.019	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.Pro568=
Coding: c.1704C>A
MANE Select: NM_000264
Type: single nucleotide variant
Location: chr9:95476058 (GRCh38)
Gene constraint: LOEUF 0.146 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 74.36 · 16 PDB
Residue 568: an α-helix; the ssd domain

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

Similar variants

PTCH1 p.Pro568Leu Uncertain significance ★ ⚠ same residue
PTCH1 p.Pro568Ser Uncertain significance ★ ⚠ same residue
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
PTCH1 c.202-2A>C Pathogenic/Likely pathogenic ★★ same condition
PTCH1 c.202-2A>G Pathogenic ★★ same condition
PTCH1 c.394+1G>A 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-pro568 (accessed [today's date]).

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