Is CTSC p.Tyr438= (c.1314C>T) pathogenic?

CTSC p.Tyr438= (c.1314C>T) is classified Conflicting classifications of pathogenicity in CTSC (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-18). Rare (popmax 0.11%, sas); Associated with periodontitis, aggressive.

What condition is associated with CTSC p.Tyr438= (c.1314C>T)?

CTSC p.Tyr438= (c.1314C>T) is associated with periodontitis, aggressive, Papillon-Lefevre disease, Haim-Munk syndrome (ClinVar).

How common is CTSC p.Tyr438= (c.1314C>T) in the general population?

CTSC p.Tyr438= (c.1314C>T) is rare (popmax 0.11%, sas) (gnomAD).

CTSC p.Tyr438=

c.1314C>T · rs143736590 · VCV306417

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.11%, sas)

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 5.2	GERP 1.7, phastCons 1
Overall
CADD	7.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.11% South Asian · 100/91,076 alleles

Filtering AF 0.0923% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0858%

Overall 0.0713% 1,150/1,614,012 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.11%	911
Middle Eastern	0.099%	1,010
Remaining individualsnot grpmax-eligible	0.096%	1,042
European (non-Finnish)	0.0814%	1,229
African / African-American	0.02%	5,000
Admixed American	0.00834%	11,995
Finnishnot grpmax-eligible	0.00625%	15,998

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.Tyr438=
Coding: c.1314C>T
MANE Select: NM_001814
dbSNP: rs143736590
Type: single nucleotide variant
Location: chr11:88294084 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.64 · 18 PDB
Residue 438: a β-strand

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 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-tyr438 (accessed [today's date]).

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