Is CTSC p.His208fs (c.622_628del) pathogenic?

CTSC p.His208fs (c.622628del) is classified Pathogenic in CTSC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-02). Absent from gnomAD; Associated with Papillon-Lefevre disease.

What condition is associated with CTSC p.His208fs (c.622_628del)?

CTSC p.His208fs (c.622_628del) is associated with Papillon-Lefevre disease (ClinVar).

How common is CTSC p.His208fs (c.622_628del) in the general population?

CTSC p.His208fs (c.622_628del) is absent from gnomAD (gnomAD).

How is Papillon-Lefèvre syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CTSC p.His208fs

c.622_628del · rs2496555907 · VCV2446400

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

Papillon-Lefevre disease

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 4 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.9	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.His208fs
Coding: c.622_628del
MANE Select: NM_001814
dbSNP: rs2496555907
Type: Deletion
Location: chr11:88309176 (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

Papillon-Lefevre disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Papillon-Lefèvre syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

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
CTSC p.Cys136fs 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-his208fs (accessed [today's date]).

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