Is GALC p.Pro655fs (c.1964del) pathogenic?

GALC p.Pro655fs (c.1964del) is classified Pathogenic in GALC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-18). No gnomAD frequency available for this variant; Associated with Krabbe disease.

What condition is associated with GALC p.Pro655fs (c.1964del)?

GALC p.Pro655fs (c.1964del) is associated with Krabbe disease (ClinVar).

How common is GALC p.Pro655fs (c.1964del) in the general population?

GALC p.Pro655fs (c.1964del) is no gnomAD frequency available for this variant (gnomAD).

How is Krabbe disease inherited?

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

GALC p.Pro655fs

c.1964del · rs2139925832 · VCV1298354

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Krabbe disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (17 of 17) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.6	GERP -4.5

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GALC
Protein: p.Pro655fs
Coding: c.1964del
MANE Select: NM_000153
dbSNP: rs2139925832
Type: Deletion
Location: chr14:87934826 (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.1488_1489+2del Pathogenic/Likely pathogenic ★★ same condition
GALC p.Ala579fs Pathogenic ★★ same condition
GALC p.Ala618fs Pathogenic/Likely pathogenic ★★ same condition
GALC p.Asn167fs Pathogenic ★★ same condition
GALC p.Glu338fs Pathogenic ★★ same condition
GALC p.Gly52fs Pathogenic/Likely pathogenic ★★ same condition
GALC p.Gly59fs Pathogenic ★★ same condition
GALC p.Ile144fs 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-pro655fs (accessed [today's date]).

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