Is PTCH2 p.His54= (c.162T>C) pathogenic?

PTCH2 p.His54= (c.162T>C) is classified Likely benign in PTCH2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-26). Ultra-rare (popmax 0.0164%, mid); Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with PTCH2 p.His54= (c.162T>C)?

PTCH2 p.His54= (c.162T>C) is associated with nevoid basal cell carcinoma syndrome (ClinVar).

How common is PTCH2 p.His54= (c.162T>C) in the general population?

PTCH2 p.His54= (c.162T>C) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

PTCH2 p.His54=

c.162T>C · rs375847993 · VCV1084738

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 3.9	GERP -1.9, phastCons 1
Overall
CADD	8.699	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00533%

Overall 0.0057% 92/1,614,104 alleles · ultra-rare exomes 89/1,461,870 · genomes 3/152,234 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.00703%	14,217
Remaining individualsnot grpmax-eligible	0.0064%	15,622
African / African-American	0.00267%	37,476
Admixed American	0.00167%	60,014
South Asian	0.0011%	91,088

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.His54=
Coding: c.162T>C
MANE Select: NM_003738
dbSNP: rs375847993
Type: single nucleotide variant
Location: chr1:44841950 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25
Residue 54: the 'pre-tm1' 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-his54 (accessed [today's date]).

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