Is CTSC p.Ter464= (c.1392G>A) pathogenic?

CTSC p.Ter464= (c.1392G>A) is classified Likely benign in CTSC (ClinVar, Single submitter, 2 submitters; last evaluated 2025-08-14). Rare (popmax 0.1%, afr); Associated with Papillon-Lefevre disease.

What condition is associated with CTSC p.Ter464= (c.1392G>A)?

CTSC p.Ter464= (c.1392G>A) is associated with Papillon-Lefevre disease, Haim-Munk syndrome, CTSC-related disorder (ClinVar).

How common is CTSC p.Ter464= (c.1392G>A) in the general population?

CTSC p.Ter464= (c.1392G>A) is rare (popmax 0.1%, afr) (gnomAD).

How is Papillon-Lefèvre syndrome inherited?

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

CTSC p.Ter464=

c.1392G>A · rs143054754 · VCV650803

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.1%, afr)

Conditions

Papillon-Lefevre disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.49	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 0.55	GERP 0.7, phastCons 0.22
Overall
CADD	7.111	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 0.1% African / African-American · 75/74,994 alleles

Filtering AF 0.0817% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0751%

Overall 0.00508% 82/1,613,884 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.1%	1,000
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0048%	20,836
Admixed American	0.00167%	59,986
South Asian	0.0011%	91,078
European (non-Finnish)	8.47e-05%	1,179,970

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.Ter464=
Coding: c.1392G>A
MANE Select: NM_001814
dbSNP: rs143054754
Type: single nucleotide variant
Location: chr11:88294006 (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

Also linked: Haim-Munk syndrome CTSC-related disorder periodontitis, aggressive

For Papillon-Lefèvre syndrome (Orphanet):

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

Similar variants

CTSC c.319-1G>A Pathogenic ★★ same condition
CTSC c.757+1G>T Likely pathogenic ★★ same condition
CTSC c.-55C>A Pathogenic ★★ same condition
CTSC p.Arg210Ter Pathogenic ★★ same condition
CTSC p.Arg250Ter Pathogenic/Likely pathogenic ★★ same condition
CTSC p.Arg272His Pathogenic/Likely pathogenic ★★ ⚠ same condition
CTSC p.Arg272Pro Pathogenic/Likely pathogenic ★★ same condition
CTSC p.Arg339Cys Pathogenic/Likely 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-ter464 (accessed [today's date]).

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