Is CTSD p.Val52fs (c.153del) pathogenic?

CTSD p.Val52fs (c.153del) is classified Pathogenic/Likely pathogenic in CTSD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-09-22). Very rare (popmax 0.00133%, afr); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CTSD p.Val52fs (c.153del)?

CTSD p.Val52fs (c.153del) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CTSD p.Val52fs (c.153del) in the general population?

CTSD p.Val52fs (c.153del) is very rare (popmax 0.00133%, afr) (gnomAD).

CTSD p.Val52fs

c.153del · rs35855065 · VCV2419916

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

neuronal ceroid lipofuscinosis

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 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.1	GERP -2
Overall
CADD	18.06	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,928 alleles

Overall 0.000657% 1/152,196 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: CTSD
Protein: p.Val52fs
Coding: c.153del
MANE Select: NM_001909
dbSNP: rs35855065
Type: Deletion
Location: chr11:1761384 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.69 · 9 PDB

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

Disease context

neuronal ceroid lipofuscinosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTSD p.Val52Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
CTSD p.Gln90fs Pathogenic/Likely pathogenic ★★ same condition
CTSD p.Val318fs Pathogenic/Likely pathogenic ★★ same condition
CTSD p.Pro381fs Uncertain significance ★★ same condition
CTSD c.828-14_828-13del Benign/Likely benign ★★ same condition
CTSD c.824_827+30del Likely pathogenic ★ same condition
CTSD p.Ala18fs Pathogenic ★ same condition
CTSD p.Ala317fs 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/ctsd-p-val52fs (accessed [today's date]).

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