Is CTSK p.Phe142fs (c.426del) pathogenic?

CTSK p.Phe142fs (c.426del) is classified Pathogenic in CTSK (ClinVar, Single submitter, 2 submitters; last evaluated 2023-07-24). Very rare (popmax 0.00891%, eas); Associated with pycnodysostosis.

What condition is associated with CTSK p.Phe142fs (c.426del)?

CTSK p.Phe142fs (c.426del) is associated with pycnodysostosis (ClinVar).

How common is CTSK p.Phe142fs (c.426del) in the general population?

CTSK p.Phe142fs (c.426del) is very rare (popmax 0.00891%, eas) (gnomAD).

How is Pycnodysostosis inherited?

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

CTSK p.Phe142fs

c.426del · rs1057516514 · VCV370473

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Conditions

pycnodysostosis

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 5 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,876 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000274% 4/1,461,876 alleles · very rare

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: CTSK
Protein: p.Phe142fs
Coding: c.426del
MANE Select: NM_000396
dbSNP: rs1057516514
Type: Deletion
Location: chr1:150804213 (GRCh38)
Gene constraint: LOEUF 0.748 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.89 · 70 PDB
Residue 142: an α-helix; a disulfide bond

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

Disease context

pycnodysostosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Pycnodysostosis (Orphanet):

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

Similar variants

CTSK p.Ala64fs Pathogenic/Likely pathogenic ★★ same condition
CTSK p.Asn273fs Pathogenic/Likely pathogenic ★★ same condition
CTSK p.Gln165fs Pathogenic ★★ same condition
CTSK p.Gly113fs Pathogenic/Likely pathogenic ★★ same condition
CTSK p.Leu4fs Likely pathogenic ★★ same condition
CTSK p.Leu97fs Pathogenic/Likely pathogenic ★★ same condition
CTSK p.Tyr17fs Pathogenic/Likely pathogenic ★★ same condition
CTSK c.239_243+1del 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/ctsk-p-phe142fs (accessed [today's date]).

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