Is PTCH2 p.Asp644fs (c.1930_1931insGGGGGGG) pathogenic?

PTCH2 p.Asp644fs (c.19301931insGGGGGGG) is classified Uncertain significance in PTCH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-08). Very rare (popmax 0.000678%, nfe); Associated with nevoid basal cell carcinoma syndrome.

What condition is associated with PTCH2 p.Asp644fs (c.1930_1931insGGGGGGG)?

PTCH2 p.Asp644fs (c.1930_1931insGGGGGGG) is associated with nevoid basal cell carcinoma syndrome (ClinVar).

How common is PTCH2 p.Asp644fs (c.1930_1931insGGGGGGG) in the general population?

PTCH2 p.Asp644fs (c.1930_1931insGGGGGGG) is very rare (popmax 0.000678%, nfe) (gnomAD).

PTCH2 p.Asp644fs

c.1930_1931insGGGGGGG · rs762665624 · VCV2746674

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

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 14 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.4, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,180,020 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,614,100 alleles · very rare exomes 7/1,461,862 · genomes 1/152,238 · joint denominator

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.Asp644fs
Coding: c.1930_1931insGGGGGGG
MANE Select: NM_003738
dbSNP: rs762665624
Type: Insertion
Location: chr1:44827970 (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.Asp644Glu Uncertain significance ★ ⚠ same residue
PTCH2 c.3258-6_3258-5insTAGTA Uncertain significance ★ same condition
PTCH2 p.Lys889fs Uncertain significance ★ same condition
PTCH2 p.Thr975_Phe976insAla Uncertain significance ★ same condition
PTCH2 p.Val399_Gly400insVal Uncertain significance ★ same condition
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

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-asp644fs (accessed [today's date]).

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