Is PTCH2 p.Val433fs (c.1296_1305delinsCACCA) pathogenic?

PTCH2 p.Val433fs (c.12961305delinsCACCA) is classified Conflicting classifications of pathogenicity in PTCH2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-06-18). No gnomAD frequency available for this variant; Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with PTCH2 p.Val433fs (c.1296_1305delinsCACCA)?

PTCH2 p.Val433fs (c.1296_1305delinsCACCA) is associated with nevoid basal cell carcinoma syndrome, basal cell nevus syndrome 1 (ClinVar).

How common is PTCH2 p.Val433fs (c.1296_1305delinsCACCA) in the general population?

PTCH2 p.Val433fs (c.1296_1305delinsCACCA) is no gnomAD frequency available for this variant (gnomAD).

PTCH2 p.Val433fs

c.1296_1305delinsCACCA · rs1573648653 · VCV651390

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

nevoid basal cell carcinoma syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.2	GERP -0.17, phastCons 0.97
Region caveats
Repeat context	tandem	G-rich low complexity · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PTCH2
Protein: p.Val433fs
Coding: c.1296_1305delinsCACCA
MANE Select: NM_003738
dbSNP: rs1573648653
Type: Indel
Location: chr1:44829223 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25
Residue 433: 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

Also linked: basal cell nevus syndrome 1

Similar variants

PTCH2 p.Val433Met Uncertain significance ★ ⚠ same residue
PTCH2 c.3258-5_3258-3delinsTAGTACCTAGG Uncertain significance ★ same condition
PTCH2 p.Asp829Val Uncertain significance ★ same condition
PTCH2 p.Leu731Gln Uncertain significance ★ same condition
PTCH2 p.Leu982Gly Uncertain significance ★ same condition
PTCH2 p.Lys686Glu Uncertain significance ★ same condition
PTCH2 p.Ser837Ile Uncertain significance ★ same condition
PTCH2 p.Ser949Asn 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-val433fs (accessed [today's date]).

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