Is CTSA p.Arg37Pro (c.110G>C) pathogenic?

CTSA p.Arg37Pro (c.110G>C) is classified Uncertain significance in CTSA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-29). AlphaMissense: ambiguous (0.5131); Very rare (popmax 0.000763%, nfe); Associated with galactosialidosis.

What condition is associated with CTSA p.Arg37Pro (c.110G>C)?

CTSA p.Arg37Pro (c.110G>C) is associated with galactosialidosis (ClinVar).

How common is CTSA p.Arg37Pro (c.110G>C) in the general population?

CTSA p.Arg37Pro (c.110G>C) is very rare (popmax 0.000763%, nfe) (gnomAD).

How is Galactosialidosis inherited?

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

What do computational predictors say about CTSA p.Arg37Pro (c.110G>C)?

AlphaMissense predicts ambiguous (score 0.5131) — an in-silico prediction, not a clinical call.

CTSA p.Arg37Pro

c.110G>C · rs751427255 · VCV1408753

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5131 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Conditions

galactosialidosis

Computational evidence

Protein change
AlphaMissense	0.5131	ambiguous
REVEL	0.517	indeterminate
SaProt	LLR -11.64	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.072	GERP -3.9
Regional constraint	o/e 0.92	unconstrained · MANE · 1,710 bp · p 0.19 · regional, not allelic
Overall
CADD	6.685	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,179,960 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000558% 9/1,612,746 alleles · very rare exomes 8/1,460,750 · genomes 1/151,996 · joint denominator

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.Arg37Pro
Coding: c.110G>C
MANE Select: NM_000308
dbSNP: rs751427255
Type: single nucleotide variant
Location: chr20:45891678 (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.Arg37= Likely benign ★ 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-arg37pro (accessed [today's date]).

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