Is GALC p.Val175= (c.525C>T) pathogenic?

GALC p.Val175= (c.525C>T) is classified Conflicting classifications of pathogenicity in GALC (ClinVar, Conflicting submitters, 13 submitters; last evaluated 2026-05-01). Rare (popmax 0.355%, nfe); Associated with Krabbe disease.

What condition is associated with GALC p.Val175= (c.525C>T)?

GALC p.Val175= (c.525C>T) is associated with Krabbe disease (ClinVar).

How common is GALC p.Val175= (c.525C>T) in the general population?

GALC p.Val175= (c.525C>T) is rare (popmax 0.355%, nfe) (gnomAD).

How is Krabbe disease inherited?

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

GALC p.Val175=

c.525C>T · rs181066089 · VCV496798

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 13 submitters

gnomAD v4.1

Rare

rare (popmax 0.355%, 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 -0.29	GERP -5.1
Overall
CADD	5.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.355% European (non-Finnish) · 4,188/1,179,932 alleles

Filtering AF 0.346% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.342%

Overall 0.288% 4,656/1,614,016 alleles · rare exomes 4,378/1,461,760 · genomes 278/152,256 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.355%	282
Finnishnot grpmax-eligible	0.326%	306
Remaining individualsnot grpmax-eligible	0.224%	446
Ashkenazi Jewishnot grpmax-eligible	0.111%	897
Admixed American	0.06%	1,667
African / African-American	0.056%	1,786
Middle Eastern	0.033%	3,031
South Asian	0.00659%	15,179

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.Val175=
Coding: c.525C>T
MANE Select: NM_000153
dbSNP: rs181066089
Type: single nucleotide variant
Location: chr14:87984451 (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.Val175Ile 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
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-val175 (accessed [today's date]).

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