Is CTSA p.Pro86= (c.258C>T) pathogenic?

CTSA p.Pro86= (c.258C>T) is classified Likely benign in CTSA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-07). Ultra-rare (popmax 0.0165%, sas); Associated with galactosialidosis.

What condition is associated with CTSA p.Pro86= (c.258C>T)?

CTSA p.Pro86= (c.258C>T) is associated with galactosialidosis (ClinVar).

How common is CTSA p.Pro86= (c.258C>T) in the general population?

CTSA p.Pro86= (c.258C>T) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

How is Galactosialidosis inherited?

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

CTSA p.Pro86=

c.258C>T · rs766977905 · VCV2881241

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

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 -6.2	GERP -3.9
Overall
CADD	2.768	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% South Asian · 15/91,084 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.000991% 16/1,614,118 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0165%	6,072
Remaining individualsnot grpmax-eligible	0.0016%	62,508

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.Pro86=
Coding: c.258C>T
MANE Select: NM_000308
dbSNP: rs766977905
Type: single nucleotide variant
Location: chr20:45891979 (GRCh38)
Gene constraint: LOEUF 0.851 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.59 · 12 PDB
Residue 86: 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

Similar variants

CTSA p.Pro86Leu Uncertain significance ★ ⚠ same residue
CTSA p.Pro86fs 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-pro86 (accessed [today's date]).

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