Is GALC p.Arg53= (c.157C>A) pathogenic?

GALC p.Arg53= (c.157C>A) is classified Uncertain significance in GALC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-23). Very rare (popmax 8.69e-05%, nfe); Associated with Krabbe disease.

What condition is associated with GALC p.Arg53= (c.157C>A)?

GALC p.Arg53= (c.157C>A) is associated with Krabbe disease (ClinVar).

How common is GALC p.Arg53= (c.157C>A) in the general population?

GALC p.Arg53= (c.157C>A) is very rare (popmax 8.69e-05%, nfe) (gnomAD).

How is Krabbe disease inherited?

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

GALC p.Arg53=

c.157C>A · rs752371343 · VCV1881562

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.69e-05%, nfe)

Conditions

Krabbe disease

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 0.48, phastCons 1
Overall
CADD	15.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.69e-05% European (non-Finnish) · 1/1,151,112 alleles

Overall 6.49e-05% 1/1,540,884 alleles · very rare exomes 1/1,388,626 · genomes 0/152,258 · 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: GALC
Protein: p.Arg53=
Coding: c.157C>A
MANE Select: NM_000153
dbSNP: rs752371343
Type: single nucleotide variant
Location: chr14:87993008 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.56

Full GALC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Krabbe disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Krabbe disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

GALC p.Arg53Gln Uncertain significance ★ ⚠ same residue
GALC p.Arg53Trp Uncertain significance ★ ⚠ same residue
GALC c.1033+1G>A Likely pathogenic ★★ same condition
GALC c.1034-1G>C Pathogenic/Likely pathogenic ★★ same condition
GALC c.1034-2A>G Pathogenic/Likely pathogenic ★★ same condition
GALC c.1161+2T>A Likely pathogenic ★★ same condition
GALC c.1251+1G>C Pathogenic/Likely pathogenic ★★ same condition
GALC c.1252-1G>C 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/galc-p-arg53 (accessed [today's date]).

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