Is CTSA p.Pro8Leu (c.23C>T) pathogenic?

CTSA p.Pro8Leu (c.23C>T) is classified Uncertain significance in CTSA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-19). AlphaMissense: likely benign (0.0978); Absent from gnomAD v4.1; Associated with galactosialidosis.

What condition is associated with CTSA p.Pro8Leu (c.23C>T)?

CTSA p.Pro8Leu (c.23C>T) is associated with galactosialidosis (ClinVar).

How common is CTSA p.Pro8Leu (c.23C>T) in the general population?

CTSA p.Pro8Leu (c.23C>T) is absent from gnomAD v4.1 (gnomAD).

How is Galactosialidosis inherited?

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

What do computational predictors say about CTSA p.Pro8Leu (c.23C>T)?

AlphaMissense predicts likely benign (score 0.0978) — an in-silico prediction, not a clinical call.

CTSA p.Pro8Leu

c.23C>T · VCV4797086

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0978 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,572,864)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

galactosialidosis

Computational evidence

Protein change
AlphaMissense	0.0978	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -3.59	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 0.56	GERP -1.5, phastCons 0.058
Regional constraint	o/e 0.92	unconstrained · MANE · 1,710 bp · p 0.19 · regional, not allelic
Overall
CADD	9.685	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

No allele count reported in gnomAD v4.1 (AN 1,572,864). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CTSA
Protein: p.Pro8Leu
Coding: c.23C>T
MANE Select: NM_000308
Type: single nucleotide variant
Location: chr20:45891591 (GRCh38)
Gene constraint: LOEUF 0.851 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.59 · 12 PDB

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

Disease context

galactosialidosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Galactosialidosis (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

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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/ctsa-p-pro8leu (accessed [today's date]).

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