Is CTSC p.Tyr310= (c.930C>T) pathogenic?

CTSC p.Tyr310= (c.930C>T) is classified Likely benign in CTSC (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-19). Ultra-rare (popmax 0.0164%, mid); Associated with Haim-Munk syndrome.

What condition is associated with CTSC p.Tyr310= (c.930C>T)?

CTSC p.Tyr310= (c.930C>T) is associated with Haim-Munk syndrome, Papillon-Lefevre disease, periodontitis, aggressive (ClinVar).

How common is CTSC p.Tyr310= (c.930C>T) in the general population?

CTSC p.Tyr310= (c.930C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Haim-Munk syndrome inherited?

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

CTSC p.Tyr310=

c.930C>T · rs148742372 · VCV735220

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

Haim-Munk syndrome

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 -11	GERP -3.8
Overall
CADD	0.079	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.00969% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00905%

Overall 0.00898% 145/1,614,006 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
Remaining individualsnot grpmax-eligible	0.0144%	6,943
European (non-Finnish)	0.0113%	8,872
African / African-American	0.00267%	37,462

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.Tyr310=
Coding: c.930C>T
MANE Select: NM_001814
dbSNP: rs148742372
Type: single nucleotide variant
Location: chr11:88294468 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.64 · 18 PDB
Residue 310: a disulfide bond; an α-helix

Full CTSC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Haim-Munk syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Papillon-Lefevre disease periodontitis, aggressive

For Haim-Munk syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

CTSC p.Tyr310Ter 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
CTSC p.Arg272Pro 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-tyr310 (accessed [today's date]).

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