Is GALC p.Ala60= (c.180G>T) pathogenic?

GALC p.Ala60= (c.180G>T) is classified Likely benign in GALC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-30). Very rare (popmax 0.000262%, nfe); Associated with Krabbe disease.

What condition is associated with GALC p.Ala60= (c.180G>T)?

GALC p.Ala60= (c.180G>T) is associated with Krabbe disease (ClinVar).

How common is GALC p.Ala60= (c.180G>T) in the general population?

GALC p.Ala60= (c.180G>T) is very rare (popmax 0.000262%, nfe) (gnomAD).

How is Krabbe disease inherited?

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

GALC p.Ala60=

c.180G>T · rs1887278296 · VCV1102557

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000262%, nfe)

Conditions

Krabbe disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.21	donor loss at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP -3.8	GERP -4.3
Overall
CADD	9.264	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000262% European (non-Finnish) · 3/1,146,692 alleles

Filtering AF 7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000196% 3/1,527,958 alleles · very rare exomes 3/1,375,858 · genomes 0/152,100 · 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.Ala60=
Coding: c.180G>T
MANE Select: NM_000153
dbSNP: rs1887278296
Type: single nucleotide variant
Location: chr14:87992985 (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 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
GALC c.1671-1G>A 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-ala60 (accessed [today's date]).

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