Is PTCH2 p.Pro11Ser (c.31C>T) pathogenic?

PTCH2 p.Pro11Ser (c.31C>T) is classified Uncertain significance in PTCH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). AlphaMissense: likely benign (0.0834); Very rare (popmax 0.00119%, sas); Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with PTCH2 p.Pro11Ser (c.31C>T)?

PTCH2 p.Pro11Ser (c.31C>T) is associated with nevoid basal cell carcinoma syndrome (ClinVar).

How common is PTCH2 p.Pro11Ser (c.31C>T) in the general population?

PTCH2 p.Pro11Ser (c.31C>T) is very rare (popmax 0.00119%, sas) (gnomAD).

What do computational predictors say about PTCH2 p.Pro11Ser (c.31C>T)?

AlphaMissense predicts likely benign (score 0.0834) — an in-silico prediction, not a clinical call.

PTCH2 p.Pro11Ser

c.31C>T · rs1573666565 · VCV639196

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0834 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nevoid basal cell carcinoma syndrome

Computational evidence

Protein change
AlphaMissense	0.0834	likely benign
REVEL	0.23	benign-leaning
SaProt	LLR -7.00	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 3.6	GERP -0.98, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 21 kb · p 3.4e-06 · regional, not allelic
Overall
CADD	20.9	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 0.00119% South Asian · 1/83,826 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000194% 3/1,550,164 alleles · very rare exomes 3/1,397,848 · genomes 0/152,316 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00119%	83,826
European (non-Finnish)	0.000174%	573,158

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.Pro11Ser
Coding: c.31C>T
MANE Select: NM_003738
dbSNP: rs1573666565
Type: single nucleotide variant
Location: chr1:44842902 (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

Similar variants

PTCH2 p.Pro11= Likely benign ★ same residue
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

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-pro11ser (accessed [today's date]).

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