Is CTSC p.Leu7fs (c.21del) pathogenic?

CTSC p.Leu7fs (c.21del) is classified Pathogenic in CTSC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-26). Very rare (popmax 0.00115%, sas); Associated with periodontitis, aggressive.

What condition is associated with CTSC p.Leu7fs (c.21del)?

CTSC p.Leu7fs (c.21del) is associated with periodontitis, aggressive, Papillon-Lefevre disease, Haim-Munk syndrome (ClinVar).

How common is CTSC p.Leu7fs (c.21del) in the general population?

CTSC p.Leu7fs (c.21del) is very rare (popmax 0.00115%, sas) (gnomAD).

CTSC p.Leu7fs

c.21del · rs2496632149 · VCV2925494

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00115%, sas)

Conditions

periodontitis, aggressive

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 1 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.097	GERP -0.34

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00115% South Asian · 1/86,642 alleles

Overall 7e-05% 1/1,429,062 alleles · very rare

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: CTSC
Protein: p.Leu7fs
Coding: c.21del
MANE Select: NM_001814
dbSNP: rs2496632149
Type: Deletion
Location: chr11:88337652 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.64 · 18 PDB

Full CTSC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

periodontitis, aggressive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Papillon-Lefevre disease Haim-Munk syndrome

Similar variants

CTSC p.Leu7Phe Uncertain significance ★ ⚠ same residue
CTSC p.Leu7= Likely benign ★ same residue
CTSC p.Leu381fs Pathogenic ★★ same condition
CTSC p.Lys63_Val64insTer Pathogenic/Likely pathogenic ★★ same condition
CTSC p.Thr189fs Pathogenic ★★ same condition
CTSC c.173-7del Benign/Likely benign ★★ same condition
CTSC c.486-25_492del Likely pathogenic ★ same condition
CTSC p.Ala417fs Pathogenic ★ 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/ctsc-p-leu7fs (accessed [today's date]).

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