Is PTCH2 p.Phe671= (c.2013C>T) pathogenic?

PTCH2 p.Phe671= (c.2013C>T) is classified Benign/Likely benign in PTCH2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-04-01). Rare (popmax 0.205%, amr); Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with PTCH2 p.Phe671= (c.2013C>T)?

PTCH2 p.Phe671= (c.2013C>T) is associated with nevoid basal cell carcinoma syndrome (ClinVar).

How common is PTCH2 p.Phe671= (c.2013C>T) in the general population?

PTCH2 p.Phe671= (c.2013C>T) is rare (popmax 0.205%, amr) (gnomAD).

PTCH2 p.Phe671=

c.2013C>T · rs112563011 · VCV695301

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.205%, amr)

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 -4.9	GERP -2.8
Overall
CADD	0.098	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.205% Admixed American · 123/60,026 alleles

Filtering AF 0.175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.164%

Overall 0.112% 1,809/1,614,168 alleles · rare exomes 1,642/1,461,816 · genomes 167/152,352 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.205%	488
East Asian	0.178%	561
European (non-Finnish)	0.126%	792
Remaining individualsnot grpmax-eligible	0.0912%	1,097
Middle Eastern	0.066%	1,516
Ashkenazi Jewishnot grpmax-eligible	0.0642%	1,558
Finnishnot grpmax-eligible	0.0234%	4,265
African / African-American	0.0173%	5,774
South Asian	0.00878%	11,386

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.Phe671=
Coding: c.2013C>T
MANE Select: NM_003738
dbSNP: rs112563011
Type: single nucleotide variant
Location: chr1:44827888 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25
Residue 671: the 'pre-tm7' region

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-phe671 (accessed [today's date]).

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