Is CTSC p.His382= (c.1146C>T) pathogenic?

CTSC p.His382= (c.1146C>T) is classified Benign/Likely benign in CTSC (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-04-01). Rare (popmax 0.363%, mid); Associated with periodontitis, aggressive.

What condition is associated with CTSC p.His382= (c.1146C>T)?

CTSC p.His382= (c.1146C>T) is associated with periodontitis, aggressive, Papillon-Lefevre disease, Haim-Munk syndrome (ClinVar).

How common is CTSC p.His382= (c.1146C>T) in the general population?

CTSC p.His382= (c.1146C>T) is rare (popmax 0.363%, mid) (gnomAD).

CTSC p.His382=

c.1146C>T · rs45558734 · VCV306419

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.363%, mid)

Conditions

periodontitis, aggressive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 1, phastCons 1
Overall
CADD	6.342	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.363% Middle Eastern · 22/6,058 alleles

Filtering AF 0.347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.343%

Overall 0.288% 4,649/1,614,044 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.363%	275
European (non-Finnish)	0.356%	281
Remaining individualsnot grpmax-eligible	0.261%	383
Admixed American	0.202%	496
Ashkenazi Jewishnot grpmax-eligible	0.122%	822
Finnishnot grpmax-eligible	0.0625%	1,601
African / African-American	0.0573%	1,744
South Asian	0.022%	4,554
East Asian	0.00223%	44,860

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.His382=
Coding: c.1146C>T
MANE Select: NM_001814
dbSNP: rs45558734
Type: single nucleotide variant
Location: chr11:88294252 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.64 · 18 PDB
Residue 382: an α-helix

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.His382Arg Uncertain significance ★ ⚠ same residue
CTSC p.His382_Tyr383insTer Pathogenic ★ same residue
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

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-his382 (accessed [today's date]).

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