Is CTSA p.Pro73= (c.219C>T) pathogenic?

CTSA p.Pro73= (c.219C>T) is classified Likely benign in CTSA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-20). Very rare (popmax 0.00223%, eas); Associated with galactosialidosis.

What condition is associated with CTSA p.Pro73= (c.219C>T)?

CTSA p.Pro73= (c.219C>T) is associated with galactosialidosis (ClinVar).

How common is CTSA p.Pro73= (c.219C>T) in the general population?

CTSA p.Pro73= (c.219C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Galactosialidosis inherited?

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

CTSA p.Pro73=

c.219C>T · rs742035 · VCV1597250

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 -2.2	GERP -3.6
Overall
CADD	8.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,876 alleles

Overall 0.000186% 3/1,613,954 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,876
African / African-American	0.00134%	74,898
European (non-Finnish)	8.47e-05%	1,179,988

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.Pro73=
Coding: c.219C>T
MANE Select: NM_000308
dbSNP: rs742035
Type: single nucleotide variant
Location: chr20:45891940 (GRCh38)
Gene constraint: LOEUF 0.851 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.59 · 12 PDB
Residue 73: a turn

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-pro73 (accessed [today's date]).

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