Is CTSA p.Val399= (c.1197A>C) pathogenic?

CTSA p.Val399= (c.1197A>C) is classified Likely benign in CTSA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-18). Very rare (popmax 6.85e-05%); Associated with galactosialidosis.

What condition is associated with CTSA p.Val399= (c.1197A>C)?

CTSA p.Val399= (c.1197A>C) is associated with galactosialidosis (ClinVar).

How common is CTSA p.Val399= (c.1197A>C) in the general population?

CTSA p.Val399= (c.1197A>C) is very rare (popmax 6.85e-05%) (gnomAD).

How is Galactosialidosis inherited?

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

CTSA p.Val399=

c.1197A>C · rs1349370602 · VCV2769836

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

Conditions

galactosialidosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -1.6, phastCons 1
Overall
CADD	9.235	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.85e-05%

Overall 6.85e-05% 1/1,459,956 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.Val399=
Coding: c.1197A>C
MANE Select: NM_000308
dbSNP: rs1349370602
Type: single nucleotide variant
Location: chr20:45897749 (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 p.Val399Ile Uncertain significance ★ ⚠ 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
CTSA p.Cys256Ter 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-val399 (accessed [today's date]).

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