Is CTSA p.Tyr395= (c.1185T>C) pathogenic?

CTSA p.Tyr395= (c.1185T>C) is classified Likely benign in CTSA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-31). Very rare (popmax 0.0011%, sas); Associated with galactosialidosis.

What condition is associated with CTSA p.Tyr395= (c.1185T>C)?

CTSA p.Tyr395= (c.1185T>C) is associated with galactosialidosis (ClinVar).

How common is CTSA p.Tyr395= (c.1185T>C) in the general population?

CTSA p.Tyr395= (c.1185T>C) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Galactosialidosis inherited?

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

CTSA p.Tyr395=

c.1185T>C · rs2515447652 · VCV2833157

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

galactosialidosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.1	GERP -0.37, phastCons 1
Overall
CADD	10.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,008 alleles

Overall 6.86e-05% 1/1,457,752 alleles · very rare

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
Protein: p.Tyr395=
Coding: c.1185T>C
MANE Select: NM_000308
dbSNP: rs2515447652
Type: single nucleotide variant
Location: chr20:45897737 (GRCh38)
Gene constraint: LOEUF 0.851 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.59 · 12 PDB
Residue 395: a UniProt-annotated variant site (in gsl; loss of activity); a β-strand

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 p.Tyr395Cys Pathogenic/Likely pathogenic ★★ same residue
CTSA p.Tyr395_Asn396delinsTer Pathogenic ★ same residue
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

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-tyr395 (accessed [today's date]).

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