Is GALC p.Thr641Ala (c.1920_1921inv) pathogenic?

GALC p.Thr641Ala (c.19201921inv) is classified Likely benign in GALC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). Associated with Krabbe disease.

What condition is associated with GALC p.Thr641Ala (c.1920_1921inv)?

GALC p.Thr641Ala (c.1920_1921inv) is associated with Krabbe disease (ClinVar).

How is Krabbe disease inherited?

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

GALC p.Thr641Ala

c.1920_1921inv · VCV1100101

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

Krabbe disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.68	GERP -4.5, phastCons 0.012
Regional constraint	o/e 1.03	unconstrained · MANE · 58 kb · p 0.37 · regional, not allelic

Variant & gene context

Gene: GALC
Protein: p.Thr641Ala
Coding: c.1920_1921inv
MANE Select: NM_000153
Type: Inversion
Location: chr14:87934869 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.56
Residue 641: a UniProt-annotated variant site (in)

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.Thr540Met Uncertain significance ★ same condition
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
GALC c.1338+1G>C 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-thr641ala (accessed [today's date]).

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