Is CTSD p.Val95Ile (c.283G>A) pathogenic?

CTSD p.Val95Ile (c.283G>A) is classified Uncertain significance in CTSD (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-10-23). AlphaMissense: likely benign (0.0861); Very rare (popmax 0.00898%, nfe); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CTSD p.Val95Ile (c.283G>A)?

CTSD p.Val95Ile (c.283G>A) is associated with neuronal ceroid lipofuscinosis, neuronal ceroid lipofuscinosis 10 (ClinVar).

How common is CTSD p.Val95Ile (c.283G>A) in the general population?

CTSD p.Val95Ile (c.283G>A) is very rare (popmax 0.00898%, nfe) (gnomAD).

What do computational predictors say about CTSD p.Val95Ile (c.283G>A)?

AlphaMissense predicts likely benign (score 0.0861) — an in-silico prediction, not a clinical call.

CTSD p.Val95Ile

c.283G>A · rs141482597 · VCV423805

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0861 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00898%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
AlphaMissense	0.0861	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -2.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -3.2, phastCons 0.99
Regional constraint	o/e 0.87	unconstrained · MANE · 10 kb · p 0.0029 · regional, not allelic
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00898% European (non-Finnish) · 106/1,179,976 alleles

Filtering AF 0.00757% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00706%

Overall 0.00781% 126/1,613,592 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00898%	11,132
East Asian	0.00891%	11,222
Remaining individualsnot grpmax-eligible	0.008%	12,499
African / African-American	0.00799%	12,513
South Asian	0.00549%	18,218

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.Val95Ile
Coding: c.283G>A
MANE Select: NM_001909
dbSNP: rs141482597
Type: single nucleotide variant
Location: chr11:1759585 (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.Val95= Conflicting classifications of pathogenicity ★ 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-val95ile (accessed [today's date]).

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