Is CTSA p.Glu435= (c.1305G>A) pathogenic?

CTSA p.Glu435= (c.1305G>A) is classified Likely benign in CTSA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-19). Very rare (popmax 0.00983%, nfe); Associated with galactosialidosis.

What condition is associated with CTSA p.Glu435= (c.1305G>A)?

CTSA p.Glu435= (c.1305G>A) is associated with galactosialidosis (ClinVar).

How common is CTSA p.Glu435= (c.1305G>A) in the general population?

CTSA p.Glu435= (c.1305G>A) is very rare (popmax 0.00983%, nfe) (gnomAD).

How is Galactosialidosis inherited?

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

CTSA p.Glu435=

c.1305G>A · rs752195963 · VCV2059409

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00983%, nfe)

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 2.6	GERP 0.91, phastCons 1
Overall
CADD	4.595	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00983% European (non-Finnish) · 116/1,180,036 alleles

Filtering AF 0.00834% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00776%

Overall 0.00756% 122/1,614,032 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00983%	10,173
Remaining individualsnot grpmax-eligible	0.0064%	15,622
African / African-American	0.00267%	37,450

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.Glu435=
Coding: c.1305G>A
MANE Select: NM_000308
dbSNP: rs752195963
Type: single nucleotide variant
Location: chr20:45898055 (GRCh38)
Gene constraint: LOEUF 0.851 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.59 · 12 PDB
Residue 435: 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

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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-glu435 (accessed [today's date]).

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