Is CTSA p.Ile35= (c.105C>T) pathogenic?

CTSA p.Ile35= (c.105C>T) is classified Benign/Likely benign in CTSA (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-18). Rare (popmax 0.81%, afr); Associated with galactosialidosis.

What condition is associated with CTSA p.Ile35= (c.105C>T)?

CTSA p.Ile35= (c.105C>T) is associated with galactosialidosis (ClinVar).

How common is CTSA p.Ile35= (c.105C>T) in the general population?

CTSA p.Ile35= (c.105C>T) is rare (popmax 0.81%, afr) (gnomAD).

How is Galactosialidosis inherited?

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

CTSA p.Ile35=

c.105C>T · rs150140984 · VCV338524

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.81%, afr)

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 1.4	GERP -0.23, phastCons 0.94
Overall
CADD	11.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.81% African / African-American · 608/75,034 alleles

Filtering AF 0.757% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.736%

Overall 0.0421% 679/1,612,926 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.81%	123
Admixed American	0.0533%	1,876
Remaining individualsnot grpmax-eligible	0.048%	2,083
Middle Eastern	0.0165%	6,062
South Asian	0.0011%	91,082
European (non-Finnish)	0.000593%	168,567

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.Ile35=
Coding: c.105C>T
MANE Select: NM_000308
dbSNP: rs150140984
Type: single nucleotide variant
Location: chr20:45891673 (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

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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-p-ile35 (accessed [today's date]).

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