Is CTSD p.Ile315= (c.945C>T) pathogenic?

CTSD p.Ile315= (c.945C>T) is classified Likely benign in CTSD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-15). Ultra-rare (popmax 0.0319%, eas); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CTSD p.Ile315= (c.945C>T)?

CTSD p.Ile315= (c.945C>T) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CTSD p.Ile315= (c.945C>T) in the general population?

CTSD p.Ile315= (c.945C>T) is ultra-rare (popmax 0.0319%, eas) (gnomAD).

CTSD p.Ile315=

c.945C>T · rs752172496 · VCV389329

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0319%, eas)

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.023	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.8
Overall
CADD	0.714	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0319% East Asian · 8/25,106 alleles

Filtering AF 0.0158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0115%

Overall 0.00316% 44/1,391,882 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0319%	3,138
Remaining individualsnot grpmax-eligible	0.0103%	9,671
South Asian	0.00456%	21,951
European (non-Finnish)	0.00259%	38,600

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.Ile315=
Coding: c.945C>T
MANE Select: NM_001909
dbSNP: rs752172496
Type: single nucleotide variant
Location: chr11:1754021 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.69 · 9 PDB
Residue 315: an α-helix; the peptidase a1 domain

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

Similar variants

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 p.Ala10Ser Uncertain significance ★★ ⚠ same condition
CTSD p.Ala18Pro Uncertain significance ★★ ⚠ same condition
CTSD p.Ala18Thr Uncertain significance ★★ ⚠ same condition
CTSD p.Ala239Val Uncertain significance ★★ ⚠ same condition
CTSD p.Arg176Lys 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-ile315 (accessed [today's date]).

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