Is CTSC p.Glu401fs (c.1202_1214del) pathogenic?

CTSC p.Glu401fs (c.12021214del) is classified Pathogenic in CTSC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-22). Absent from gnomAD; Associated with periodontitis, aggressive.

What condition is associated with CTSC p.Glu401fs (c.1202_1214del)?

CTSC p.Glu401fs (c.1202_1214del) is associated with periodontitis, aggressive, Papillon-Lefevre disease, Haim-Munk syndrome (ClinVar).

How common is CTSC p.Glu401fs (c.1202_1214del) in the general population?

CTSC p.Glu401fs (c.1202_1214del) is absent from gnomAD (gnomAD).

CTSC p.Glu401fs

c.1202_1214del · rs2496528837 · VCV2945631

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	escapes	premature termination codon in the last exon (7 of 7) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -5.3	GERP -3.8

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: CTSC
Protein: p.Glu401fs
Coding: c.1202_1214del
MANE Select: NM_001814
dbSNP: rs2496528837
Type: Deletion
Location: chr11:88294184 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.64 · 18 PDB
Residue 401: a UniProt-annotated variant site (in)

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.Glu401Lys Uncertain significance ★★ ⚠ 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
CTSC p.Asp236fs 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-glu401fs (accessed [today's date]).

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