Is CTSD p.Val95= (c.285C>T) pathogenic?

CTSD p.Val95= (c.285C>T) is classified Conflicting classifications of pathogenicity in CTSD (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-05). Absent from gnomAD v4.1; Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CTSD p.Val95= (c.285C>T)?

CTSD p.Val95= (c.285C>T) is associated with neuronal ceroid lipofuscinosis, neuronal ceroid lipofuscinosis 10 (ClinVar).

How common is CTSD p.Val95= (c.285C>T) in the general population?

CTSD p.Val95= (c.285C>T) is absent from gnomAD v4.1 (gnomAD).

CTSD p.Val95=

c.285C>T · rs1845849997 · VCV879288

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

neuronal ceroid lipofuscinosis

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 3.3	GERP -3.7, phastCons 1
Overall
CADD	9.391	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CTSD
Protein: p.Val95=
Coding: c.285C>T
MANE Select: NM_001909
dbSNP: rs1845849997
Type: single nucleotide variant
Location: chr11:1759583 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.69 · 9 PDB
Residue 95: a disulfide bond; a β-strand; 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

Also linked: neuronal ceroid lipofuscinosis 10

Similar variants

CTSD p.Val95Ile 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.Ala18Pro Uncertain significance ★★ ⚠ same condition
CTSD p.Ala18Thr 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-val95 (accessed [today's date]).

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