Is CTSD p.Pro25= (c.75G>A) pathogenic?

CTSD p.Pro25= (c.75G>A) is classified Conflicting classifications of pathogenicity in CTSD (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-02-02). Rare (popmax 0.168%, afr); Associated with Inborn genetic diseases.

What condition is associated with CTSD p.Pro25= (c.75G>A)?

CTSD p.Pro25= (c.75G>A) is associated with Inborn genetic diseases, neuronal ceroid lipofuscinosis (ClinVar).

How common is CTSD p.Pro25= (c.75G>A) in the general population?

CTSD p.Pro25= (c.75G>A) is rare (popmax 0.168%, afr) (gnomAD).

CTSD p.Pro25=

c.75G>A · rs140563067 · VCV195156

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.168%, afr)

Conditions

Inborn genetic diseases

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 -15	GERP -2
Overall
CADD	0.298	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.168% African / African-American · 126/75,046 alleles

Filtering AF 0.144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.135%

Overall 0.00911% 147/1,613,810 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.168%	596
Admixed American	0.00666%	15,006
South Asian	0.00439%	22,769
Remaining individualsnot grpmax-eligible	0.0032%	31,247
European (non-Finnish)	0.000932%	107,271

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.Pro25=
Coding: c.75G>A
dbSNP: rs140563067
Type: single nucleotide variant
Location: chr11:1761462 (GRCh38)

Full CTSD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuronal ceroid lipofuscinosis

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-pro25 (accessed [today's date]).

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