Is CTSD c.*694G>A pathogenic?

CTSD c.694G>A is classified Uncertain significance in CTSD (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Rare (popmax 0.599%, mid); Associated with neuronal ceroid lipofuscinosis 10.

What condition is associated with CTSD c.*694G>A?

CTSD c.*694G>A is associated with neuronal ceroid lipofuscinosis 10 (ClinVar).

How common is CTSD c.*694G>A in the general population?

CTSD c.*694G>A is rare (popmax 0.599%, mid) (gnomAD).

How is CLN10 disease inherited?

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

CTSD c.*694G>A

rs751538234 · VCV303820

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.599%, mid)

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 -3.1
Overall
CADD	0.222	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.599% Middle Eastern · 2/334 alleles

Filtering AF 0.249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.224%

Overall 0.112% 175/155,588 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.599%	167
Ashkenazi Jewishnot grpmax-eligible	0.487%	206
Admixed American	0.319%	313
Remaining individualsnot grpmax-eligible	0.267%	374
European (non-Finnish)	0.118%	847
African / African-American	0.0409%	2,448

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.*694G>A
MANE Select: NM_001909
dbSNP: rs751538234
Type: single nucleotide variant
Location: chr11:1752809 (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-694g-a (accessed [today's date]).

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