Is CTSD p.Ala314Thr (c.940G>A) pathogenic?

CTSD p.Ala314Thr (c.940G>A) is classified Uncertain significance in CTSD (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.138); Absent from gnomAD v4.1; Associated with neuronal ceroid lipofuscinosis 10.

What condition is associated with CTSD p.Ala314Thr (c.940G>A)?

CTSD p.Ala314Thr (c.940G>A) is associated with neuronal ceroid lipofuscinosis 10 (ClinVar).

How common is CTSD p.Ala314Thr (c.940G>A) in the general population?

CTSD p.Ala314Thr (c.940G>A) is absent from gnomAD v4.1 (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.Ala314Thr (c.940G>A)?

AlphaMissense predicts likely benign (score 0.138) — an in-silico prediction, not a clinical call.

CTSD p.Ala314Thr

c.940G>A · rs886048065 · VCV303837

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.138 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

neuronal ceroid lipofuscinosis 10

Computational evidence

Protein change
AlphaMissense	0.138	likely benign
REVEL	0.422	indeterminate
SaProt	LLR -9.63	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 10 kb · p 0.0029 · regional, not allelic
Overall
CADD	24.8	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

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.Ala314Thr
Coding: c.940G>A
MANE Select: NM_001909
dbSNP: rs886048065
Type: single nucleotide variant
Location: chr11:1754026 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.69 · 9 PDB
Residue 314: 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 10 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CLN10 disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult, Antenatal, Infancy

Similar variants

CTSD p.Ala314= Likely benign ★ same residue
CTSD c.*210C>G Uncertain significance ★★ same condition
CTSD p.Ala239Val Uncertain significance ★★ ⚠ same condition
CTSD p.Arg411His Uncertain significance ★★ ⚠ same condition
CTSD p.Glu310Lys Uncertain significance ★★ ⚠ same condition
CTSD p.Gly316Arg Uncertain significance ★★ ⚠ same condition
CTSD p.Gly362Arg Uncertain significance ★★ ⚠ same condition
CTSD p.His273Tyr 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-ala314thr (accessed [today's date]).

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