Is PTCH2 p.Leu7Val (c.19C>G) pathogenic?

PTCH2 p.Leu7Val (c.19C>G) is classified Uncertain significance in PTCH2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-03). AlphaMissense: likely benign (0.0763); Very rare (popmax 0.00592%, amr); Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with PTCH2 p.Leu7Val (c.19C>G)?

PTCH2 p.Leu7Val (c.19C>G) is associated with nevoid basal cell carcinoma syndrome, medulloblastoma, basal cell carcinoma, susceptibility to, 1 (ClinVar).

How common is PTCH2 p.Leu7Val (c.19C>G) in the general population?

PTCH2 p.Leu7Val (c.19C>G) is very rare (popmax 0.00592%, amr) (gnomAD).

What do computational predictors say about PTCH2 p.Leu7Val (c.19C>G)?

AlphaMissense predicts likely benign (score 0.0763) — an in-silico prediction, not a clinical call.

PTCH2 p.Leu7Val

c.19C>G · rs1030456781 · VCV453931

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0763 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00592%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nevoid basal cell carcinoma syndrome

Computational evidence

Protein change
AlphaMissense	0.0763	likely benign
REVEL	0.25	benign-leaning
SaProt	LLR -6.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 21 kb · p 3.4e-06 · regional, not allelic
Overall
CADD	19.63	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00592% Admixed American · 3/50,712 alleles

Filtering AF 0.00336% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00303%

Overall 0.00349% 54/1,548,998 alleles · very rare exomes 52/1,396,776 · genomes 2/152,222 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00592%	16,904
European (non-Finnish)	0.00436%	22,920
Remaining individualsnot grpmax-eligible	0.00167%	59,990

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.Leu7Val
Coding: c.19C>G
MANE Select: NM_003738
dbSNP: rs1030456781
Type: single nucleotide variant
Location: chr1:44842914 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25

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

Also linked: medulloblastoma basal cell carcinoma, susceptibility to, 1

Similar variants

PTCH2 p.Leu7Phe Uncertain significance ★ ⚠ same residue
PTCH2 p.Leu7= Likely benign ★ same residue
PTCH2 c.2976+2T>C Uncertain significance ★★ same condition
PTCH2 c.526-2A>G Uncertain significance ★★ same condition
PTCH2 c.617+4A>T 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

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-leu7val (accessed [today's date]).

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