Is CTSA c.-2A>C pathogenic?

CTSA c.-2A>C is classified Uncertain significance in CTSA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-09). Very rare (popmax 0.00185%, amr); Associated with galactosialidosis.

What condition is associated with CTSA c.-2A>C?

CTSA c.-2A>C is associated with galactosialidosis (ClinVar).

How common is CTSA c.-2A>C in the general population?

CTSA c.-2A>C is very rare (popmax 0.00185%, amr) (gnomAD).

How is Galactosialidosis inherited?

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

CTSA c.-2A>C

rs1318047747 · VCV1984622

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00185%, amr)

Conditions

galactosialidosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.047	moderately benign-leaning
Splicing
SpliceAI	Δ0.24	donor gain · deltas
Pangolin	Δ0.32	loss · gain 0.06 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 7.1	GERP 1.9, phastCons 1
Non-coding constraint	Z 4.59	1 kb window · o/e 0.58 · regional · uncalibrated
Overall
CADD	20.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00185% Admixed American · 1/53,918 alleles

Filtering AF 6.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000254% 4/1,572,610 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00185%	53,918
European (non-Finnish)	0.000259%	386,565

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: CTSA
Coding: c.-2A>C
MANE Select: NM_000308
dbSNP: rs1318047747
Type: single nucleotide variant
Location: chr20:45891378 (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

Similar variants

CTSA c.1-2A>G Pathogenic/Likely pathogenic ★★ same condition
CTSA c.358-2A>G Likely pathogenic ★★ same condition
CTSA c.601-2A>G Pathogenic/Likely pathogenic ★★ same condition
CTSA c.692+3A>G Pathogenic ★★ same condition
CTSA c.948+1G>A Likely pathogenic ★★ same condition
CTSA p.Arg375Ter Pathogenic/Likely pathogenic ★★ same condition
CTSA p.Cys256Ter Pathogenic/Likely pathogenic ★★ same condition
CTSA p.Cys281Ter Pathogenic/Likely pathogenic ★★ 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/ctsa-c-minus-2a-c (accessed [today's date]).

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