Is CTSA p.Arg48fs (c.143del) pathogenic?

CTSA p.Arg48fs (c.143del) is classified Pathogenic in CTSA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-13). Absent from gnomAD; Associated with galactosialidosis.

What condition is associated with CTSA p.Arg48fs (c.143del)?

CTSA p.Arg48fs (c.143del) is associated with galactosialidosis (ClinVar).

How common is CTSA p.Arg48fs (c.143del) in the general population?

CTSA p.Arg48fs (c.143del) is absent from gnomAD (gnomAD).

How is Galactosialidosis inherited?

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

CTSA p.Arg48fs

c.143del · rs2515432357 · VCV2101801

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

galactosialidosis

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 2 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.8	GERP 0.85, 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: CTSA
Protein: p.Arg48fs
Coding: c.143del
MANE Select: NM_000308
dbSNP: rs2515432357
Type: Deletion
Location: chr20:45891711 (GRCh38)
Gene constraint: LOEUF 0.851 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.59 · 12 PDB

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

Disease context

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

For Galactosialidosis (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

CTSA c.445-18_447del Likely pathogenic ★★ same condition
CTSA p.Ala336fs Pathogenic/Likely pathogenic ★★ same condition
CTSA p.Cys331fs Pathogenic ★★ same condition
CTSA p.Glu166fs Pathogenic/Likely pathogenic ★★ same condition
CTSA p.Gly322_Asp323insTer Pathogenic/Likely pathogenic ★★ same condition
CTSA p.Leu126fs Pathogenic/Likely pathogenic ★★ same condition
CTSA p.Leu38fs Pathogenic/Likely pathogenic ★★ same condition
CTSA p.Tyr278fs 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/ctsa-p-arg48fs (accessed [today's date]).

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