Is CTSD p.Ala314fs (c.940dup) pathogenic?

CTSD p.Ala314fs (c.940dup) is classified Pathogenic in CTSD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-19). Very rare (popmax 8.49e-05%, nfe); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CTSD p.Ala314fs (c.940dup)?

CTSD p.Ala314fs (c.940dup) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CTSD p.Ala314fs (c.940dup) in the general population?

CTSD p.Ala314fs (c.940dup) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

CTSD p.Ala314fs

c.940dup · VCV4710281

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

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 7 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.4	phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,178,488 alleles

Overall 6.86e-05% 1/1,456,728 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.Ala314fs
Coding: c.940dup
MANE Select: NM_001909
Type: Duplication
Location: chr11:1754025 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.69 · 9 PDB
Residue 314: an α-helix; 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.Ala314= Likely benign ★ same residue
CTSD p.Leu11fs Pathogenic ★★ same condition
CTSD c.675_704+1dup Likely pathogenic ★ same condition
CTSD p.Glu352fs Pathogenic ★ same condition
CTSD p.Lys253fs Pathogenic ★ same condition
CTSD p.Val156fs Pathogenic ★ same condition
CTSD p.Val174fs Pathogenic ★ same condition
CTSD c.972+4_972+5dup Uncertain significance ★ 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-ala314fs (accessed [today's date]).

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