Is CTSD p.Thr30= (c.90G>A) pathogenic?

CTSD p.Thr30= (c.90G>A) is classified Conflicting classifications of pathogenicity in CTSD (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-06-01). Ultra-rare (popmax 0.0285%, sas); Associated with Inborn genetic diseases.

What condition is associated with CTSD p.Thr30= (c.90G>A)?

CTSD p.Thr30= (c.90G>A) is associated with Inborn genetic diseases, neuronal ceroid lipofuscinosis 10, neuronal ceroid lipofuscinosis (ClinVar).

How common is CTSD p.Thr30= (c.90G>A) in the general population?

CTSD p.Thr30= (c.90G>A) is ultra-rare (popmax 0.0285%, sas) (gnomAD).

CTSD p.Thr30=

c.90G>A · rs368529527 · VCV303841

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0285%, sas)

Conditions

Inborn genetic diseases

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 -8.4	GERP -1.6
Overall
CADD	5.632	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0285% South Asian · 26/91,094 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.0118% 191/1,613,730 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0285%	3,504
European (non-Finnish)	0.0133%	7,516
African / African-American	0.004%	24,978
Remaining individualsnot grpmax-eligible	0.0032%	31,239
Finnishnot grpmax-eligible	0.00314%	31,868
Admixed American	0.00167%	60,004

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.Thr30=
Coding: c.90G>A
MANE Select: NM_001909
dbSNP: rs368529527
Type: single nucleotide variant
Location: chr11:1761447 (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

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

Also linked: neuronal ceroid lipofuscinosis 10 neuronal ceroid lipofuscinosis

Similar variants

CTSD p.Thr30Met Uncertain significance ★★ ⚠ same residue
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.Ala116Thr Uncertain significance ★★ ⚠ same condition
CTSD p.Ala18Pro 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-thr30 (accessed [today's date]).

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