Is PTCH2 p.Asp470= (c.1410C>T) pathogenic?

PTCH2 p.Asp470= (c.1410C>T) is classified Likely benign in PTCH2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-19). Ultra-rare (popmax 0.0242%, afr); Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with PTCH2 p.Asp470= (c.1410C>T)?

PTCH2 p.Asp470= (c.1410C>T) is associated with nevoid basal cell carcinoma syndrome (ClinVar).

How common is PTCH2 p.Asp470= (c.1410C>T) in the general population?

PTCH2 p.Asp470= (c.1410C>T) is ultra-rare (popmax 0.0242%, afr) (gnomAD).

PTCH2 p.Asp470=

c.1410C>T · rs140228016 · VCV2081786

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0242%, afr)

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 · G>C here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.8	GERP -1.8, phastCons 1
Overall
CADD	5.782	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0242% African / African-American · 18/74,530 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.00213% 34/1,594,796 alleles · ultra-rare exomes 28/1,442,578 · genomes 6/152,218 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0242%	4,141
Middle Eastern	0.0166%	6,018
East Asian	0.00228%	43,922
European (non-Finnish)	0.0012%	83,612

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.Asp470=
Coding: c.1410C>T
MANE Select: NM_003738
dbSNP: rs140228016
Type: single nucleotide variant
Location: chr1:44829036 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25
Residue 470: 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 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-asp470 (accessed [today's date]).

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