Is CTSD p.Asp374= (c.1122C>T) pathogenic?

CTSD p.Asp374= (c.1122C>T) is classified Benign/Likely benign in CTSD (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-29). Ultra-rare (popmax 0.0214%, nfe); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CTSD p.Asp374= (c.1122C>T)?

CTSD p.Asp374= (c.1122C>T) is associated with neuronal ceroid lipofuscinosis, neuronal ceroid lipofuscinosis 10 (ClinVar).

How common is CTSD p.Asp374= (c.1122C>T) in the general population?

CTSD p.Asp374= (c.1122C>T) is ultra-rare (popmax 0.0214%, nfe) (gnomAD).

CTSD p.Asp374=

c.1122C>T · rs145821780 · VCV137045

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0214%, nfe)

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	phastCons 1
Overall
CADD	13.37	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0214% European (non-Finnish) · 253/1,179,908 alleles

Filtering AF 0.0193% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0184%

Overall 0.017% 274/1,612,846 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0214%	4,664
Remaining individualsnot grpmax-eligible	0.0208%	4,805
Admixed American	0.00833%	12,001
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,596
African / African-American	0.00267%	37,447

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.Asp374=
Coding: c.1122C>T
MANE Select: NM_001909
dbSNP: rs145821780
Type: single nucleotide variant
Location: chr11:1753620 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.69 · 9 PDB
Residue 374: the peptidase a1 domain; an α-helix

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

Also linked: neuronal ceroid lipofuscinosis 10

Similar variants

CTSD c.228+1G>A Likely pathogenic ★★ same condition
CTSD p.Glu82Ter Pathogenic/Likely pathogenic ★★ same condition
CTSD c.828-3C>A Uncertain significance ★★ same condition
CTSD c.*210C>G Uncertain significance ★★ same condition
CTSD p.Ala10Ser Uncertain significance ★★ ⚠ same condition
CTSD p.Ala18Pro Uncertain significance ★★ ⚠ same condition
CTSD p.Ala18Thr Uncertain significance ★★ ⚠ same condition
CTSD p.Ala239Val 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-asp374 (accessed [today's date]).

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