Is CTSD p.Pro68= (c.204C>T) pathogenic?

CTSD p.Pro68= (c.204C>T) is classified Likely benign in CTSD (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-29). Ultra-rare (popmax 0.033%, mid); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CTSD p.Pro68= (c.204C>T)?

CTSD p.Pro68= (c.204C>T) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CTSD p.Pro68= (c.204C>T) in the general population?

CTSD p.Pro68= (c.204C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

CTSD p.Pro68=

c.204C>T · rs563052262 · VCV1142613

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -14	GERP -1.7
Overall
CADD	0.053	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.00105% 17/1,613,848 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
Admixed American	0.00666%	15,006
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
Remaining individualsnot grpmax-eligible	0.0016%	62,504
Finnishnot grpmax-eligible	0.00157%	63,710
European (non-Finnish)	0.000678%	147,501

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.Pro68=
Coding: c.204C>T
dbSNP: rs563052262
Type: single nucleotide variant
Location: chr11:1761333 (GRCh38)

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

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-pro68 (accessed [today's date]).

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