Is CTSD c.*494C>T pathogenic?

CTSD c.494C>T is classified Uncertain significance in CTSD (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Ultra-rare (popmax 0.0261%, amr); Associated with neuronal ceroid lipofuscinosis 10.

What condition is associated with CTSD c.*494C>T?

CTSD c.*494C>T is associated with neuronal ceroid lipofuscinosis 10 (ClinVar).

How common is CTSD c.*494C>T in the general population?

CTSD c.*494C>T is ultra-rare (popmax 0.0261%, amr) (gnomAD).

How is CLN10 disease inherited?

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

CTSD c.*494C>T

rs551867617 · VCV877621

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0261%, amr)

Conditions

neuronal ceroid lipofuscinosis 10

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 -1.9
Overall
CADD	2.148	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0261% Admixed American · 5/19,144 alleles

Filtering AF 0.0149% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0127%

Overall 0.0174% 41/234,964 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0316%	3,169
Admixed Americangrpmax	0.0261%	3,829
European (non-Finnish)	0.0215%	4,645
Finnishnot grpmax-eligible	0.0139%	7,177
African / African-American	0.0114%	8,751
South Asian	0.0102%	9,846

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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
Coding: c.*494C>T
MANE Select: NM_001909
dbSNP: rs551867617
Type: single nucleotide variant
Location: chr11:1753009 (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 10 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CLN10 disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult, Antenatal, Infancy

Similar variants

CTSD c.*210C>G Uncertain significance ★★ same condition
CTSD p.Ala239Val Uncertain significance ★★ ⚠ same condition
CTSD p.Arg411His Uncertain significance ★★ ⚠ same condition
CTSD p.Glu310Lys Uncertain significance ★★ ⚠ same condition
CTSD p.Gly316Arg Uncertain significance ★★ ⚠ same condition
CTSD p.Gly362Arg Uncertain significance ★★ ⚠ same condition
CTSD p.His273Tyr Uncertain significance ★★ ⚠ same condition
CTSD p.Ile198Val 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-c-star-494c-t (accessed [today's date]).

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