Is CTSD p.Ser157fs (c.468_469del) pathogenic?

CTSD p.Ser157fs (c.468469del) is classified Pathogenic in CTSD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-03). Absent from gnomAD; Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CTSD p.Ser157fs (c.468_469del)?

CTSD p.Ser157fs (c.468_469del) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CTSD p.Ser157fs (c.468_469del) in the general population?

CTSD p.Ser157fs (c.468_469del) is absent from gnomAD (gnomAD).

CTSD p.Ser157fs

c.468_469del · rs2493825774 · VCV2160697

Pathogenic Single submitter

Classification

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

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 4 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP -2.9, 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: CTSD
Protein: p.Ser157fs
Coding: c.468_469del
MANE Select: NM_001909
dbSNP: rs2493825774
Type: Microsatellite
Location: chr11:1758971 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.69 · 9 PDB
Residue 157: a disulfide bond; a β-strand; the peptidase a1 domain

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.Ser157= Uncertain significance ★★ same residue
CTSD p.Ser157Leu Uncertain significance ★★ ⚠ same residue
CTSD p.Asn402del Uncertain significance ★★ same condition
CTSD p.Phe229del Conflicting classifications of pathogenicity ★ same condition
CTSD c.472-16_472-15del Likely benign ★ same condition
CTSD c.228+1G>A Likely pathogenic ★★ same condition
CTSD p.Gln90fs Pathogenic/Likely pathogenic ★★ same condition
CTSD p.Glu82Ter 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/ctsd-p-ser157fs (accessed [today's date]).

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