Is GALC p.Ala20= (c.60C>T) pathogenic?

GALC p.Ala20= (c.60C>T) is classified Likely benign in GALC (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-05). Ultra-rare (popmax 0.0463%, nfe); Associated with Krabbe disease.

What condition is associated with GALC p.Ala20= (c.60C>T)?

GALC p.Ala20= (c.60C>T) is associated with Krabbe disease (ClinVar).

How common is GALC p.Ala20= (c.60C>T) in the general population?

GALC p.Ala20= (c.60C>T) is ultra-rare (popmax 0.0463%, nfe) (gnomAD).

How is Krabbe disease inherited?

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

GALC p.Ala20=

c.60C>T · rs188488238 · VCV382304

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0463%, 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 1.3	GERP -0.45, phastCons 0.9
Overall
CADD	8.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0463% European (non-Finnish) · 541/1,167,996 alleles

Filtering AF 0.0431% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0418%

Overall 0.0353% 560/1,588,068 alleles · ultra-rare exomes 538/1,435,750 · genomes 22/152,318 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0463%	2,159
Finnishnot grpmax-eligible	0.0117%	8,540
Remaining individualsnot grpmax-eligible	0.0114%	8,782
African / African-American	0.00402%	24,888
Admixed American	0.00177%	56,644
South Asian	0.00114%	87,786

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.Ala20=
Coding: c.60C>T
MANE Select: NM_000153
dbSNP: rs188488238
Type: single nucleotide variant
Location: chr14:87993105 (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-ala20 (accessed [today's date]).

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