Is GALC p.Trp331fs (c.992_993insCT) pathogenic?

GALC p.Trp331fs (c.992993insCT) is classified Likely pathogenic in GALC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-02). Absent from gnomAD; Associated with Krabbe disease.

What condition is associated with GALC p.Trp331fs (c.992_993insCT)?

GALC p.Trp331fs (c.992_993insCT) is associated with Krabbe disease (ClinVar).

How common is GALC p.Trp331fs (c.992_993insCT) in the general population?

GALC p.Trp331fs (c.992_993insCT) is absent from gnomAD (gnomAD).

How is Krabbe disease inherited?

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

GALC p.Trp331fs

c.992_993insCT · rs2503439925 · VCV1724903

Likely pathogenic Single submitter

Classification

Likely 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	predicted	premature termination codon in exon 9 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1

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.Trp331fs
Coding: c.992_993insCT
MANE Select: NM_000153
dbSNP: rs2503439925
Type: Insertion
Location: chr14:87965545 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.56
Residue 331: a disulfide bond

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.Gly575fs Pathogenic ★★ same condition
GALC p.Leu45fs Pathogenic ★ same condition
GALC p.Lys563delinsIleLeuTer Pathogenic ★ same condition
GALC p.Tyr125fs Likely pathogenic ★ same condition
GALC p.Val61fs Pathogenic ★ same condition
GALC p.Gly63delinsGluArg Uncertain significance ★ same condition
GALC p.Trp331Arg Uncertain significance ★ ⚠ same residue
GALC c.1834+13_1834+14insA Likely benign ★ 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-trp331fs (accessed [today's date]).

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