Is CTSD p.Ala239Val (c.716C>T) pathogenic?

CTSD p.Ala239Val (c.716C>T) is classified Uncertain significance in CTSD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-07-23). AlphaMissense: likely benign (0.1332); Very rare (popmax 0.00446%, eas); Associated with neuronal ceroid lipofuscinosis 10.

What condition is associated with CTSD p.Ala239Val (c.716C>T)?

CTSD p.Ala239Val (c.716C>T) is associated with neuronal ceroid lipofuscinosis 10, neuronal ceroid lipofuscinosis (ClinVar).

How common is CTSD p.Ala239Val (c.716C>T) in the general population?

CTSD p.Ala239Val (c.716C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

How is CLN10 disease inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CTSD p.Ala239Val (c.716C>T)?

AlphaMissense predicts likely benign (score 0.1332) — an in-silico prediction, not a clinical call.

CTSD p.Ala239Val

c.716C>T · rs759564989 · VCV846960

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1332 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neuronal ceroid lipofuscinosis 10

Computational evidence

Protein change
AlphaMissense	0.1332	likely benign
REVEL	0.169	moderately benign-leaning
SaProt	LLR -11.61	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -2.7, phastCons 0.97
Regional constraint	o/e 0.87	unconstrained · MANE · 10 kb · p 0.0029 · regional, not allelic
Overall
CADD	18.59	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,886 alleles

Filtering AF 0.00165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00204% 33/1,613,716 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,443
African / African-American	0.00267%	37,428
European (non-Finnish)	0.00237%	42,139
Remaining individualsnot grpmax-eligible	0.0016%	62,478

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.Ala239Val
Coding: c.716C>T
MANE Select: NM_001909
dbSNP: rs759564989
Type: single nucleotide variant
Location: chr11:1755017 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.69 · 9 PDB
Residue 239: the peptidase a1 domain

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

Disease context

neuronal ceroid lipofuscinosis 10 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuronal ceroid lipofuscinosis

For CLN10 disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult, Antenatal, Infancy

Similar variants

CTSD p.Ala239= Likely benign ★★ 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-ala239val (accessed [today's date]).

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