Is GALC p.Arg396= (c.1188G>T) pathogenic?

GALC p.Arg396= (c.1188G>T) is classified Likely benign in GALC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-26). Very rare (popmax 0.00274%, afr); Associated with Krabbe disease.

What condition is associated with GALC p.Arg396= (c.1188G>T)?

GALC p.Arg396= (c.1188G>T) is associated with Krabbe disease (ClinVar).

How common is GALC p.Arg396= (c.1188G>T) in the general population?

GALC p.Arg396= (c.1188G>T) is very rare (popmax 0.00274%, afr) (gnomAD).

How is Krabbe disease inherited?

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

GALC p.Arg396=

c.1188G>T · rs1348158663 · VCV1126732

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00274%, afr)

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 -2.4	GERP -1.7
Overall
CADD	5.973	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00274% African / African-American · 2/72,900 alleles

Filtering AF 0.000455% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00017%

Overall 0.0005% 8/1,601,260 alleles · very rare exomes 5/1,454,576 · genomes 3/146,684 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00274%	36,450
European (non-Finnish)	0.000511%	195,524

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.Arg396=
Coding: c.1188G>T
MANE Select: NM_000153
dbSNP: rs1348158663
Type: single nucleotide variant
Location: chr14:87950722 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.56
Residue 396: a UniProt-annotated variant site (in krb); a binding site

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.Arg396Trp Pathogenic ★★ ⚠ same residue
GALC p.Arg396Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
GALC p.Arg396fs Likely pathogenic ★ same residue
GALC p.Arg396Pro 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

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-arg396 (accessed [today's date]).

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