Is GALC p.Phe577= (c.1731C>T) pathogenic?

GALC p.Phe577= (c.1731C>T) is classified Benign/Likely benign in GALC (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Low-frequency (popmax 1.37%, sas); Associated with Krabbe disease.

What condition is associated with GALC p.Phe577= (c.1731C>T)?

GALC p.Phe577= (c.1731C>T) is associated with Krabbe disease (ClinVar).

How common is GALC p.Phe577= (c.1731C>T) in the general population?

GALC p.Phe577= (c.1731C>T) is low-frequency (popmax 1.37%, sas) (gnomAD).

How is Krabbe disease inherited?

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

GALC p.Phe577=

c.1731C>T · rs201560122 · VCV314745

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.37%, sas)

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 3.5	GERP 0.48, phastCons 1
Overall
CADD	12.42	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.37% South Asian · 1,245/90,786 alleles

Filtering AF 1.31% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.28%

Overall 0.0845% 1,352/1,599,724 alleles · low-frequency exomes 1,265/1,447,742 · genomes 87/151,982 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	1.37%	73
Remaining individualsnot grpmax-eligible	0.102%	984
Admixed American	0.0401%	2,494
Middle Eastern	0.0166%	6,032
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,430
African / African-American	0.00268%	37,330
East Asian	0.00224%	44,718
European (non-Finnish)	0.00128%	77,825

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.Phe577=
Coding: c.1731C>T
MANE Select: NM_000153
dbSNP: rs201560122
Type: single nucleotide variant
Location: chr14:87941498 (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-phe577 (accessed [today's date]).

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