Is CTSK p.Ala238fs (c.712delinsTCAGGCTTGCAT) pathogenic?

CTSK p.Ala238fs (c.712delinsTCAGGCTTGCAT) is classified Likely pathogenic in CTSK (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-17). Absent from gnomAD; Associated with pycnodysostosis.

What condition is associated with CTSK p.Ala238fs (c.712delinsTCAGGCTTGCAT)?

CTSK p.Ala238fs (c.712delinsTCAGGCTTGCAT) is associated with pycnodysostosis (ClinVar).

How common is CTSK p.Ala238fs (c.712delinsTCAGGCTTGCAT) in the general population?

CTSK p.Ala238fs (c.712delinsTCAGGCTTGCAT) is absent from gnomAD (gnomAD).

How is Pycnodysostosis inherited?

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

CTSK p.Ala238fs

c.712delinsTCAGGCTTGCAT · rs2525166522 · VCV1726462

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 6 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CTSK
Protein: p.Ala238fs
Coding: c.712delinsTCAGGCTTGCAT
MANE Select: NM_000396
dbSNP: rs2525166522
Type: Indel
Location: chr1:150799616 (GRCh38)
Gene constraint: LOEUF 0.748 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.89 · 70 PDB
Residue 238: an α-helix

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.Ala115fs Likely pathogenic ★ same condition
CTSK p.Trp140fs Likely pathogenic ★ same condition
CTSK p.Ala238= Likely benign ★ same residue
CTSK p.Asn192fs Likely pathogenic same condition
CTSK c.121-1G>A Pathogenic/Likely pathogenic ★★ same condition
CTSK c.121-2A>G Pathogenic/Likely pathogenic ★★ same condition
CTSK c.244-29A>G Pathogenic/Likely pathogenic ★★ same condition
CTSK c.400-1G>C 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-ala238fs (accessed [today's date]).

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