Is GALC p.Ter686= (c.2057A>G) pathogenic?

GALC p.Ter686= (c.2057A>G) is classified Likely benign in GALC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-18). Absent from gnomAD v4.1; Associated with Krabbe disease.

What condition is associated with GALC p.Ter686= (c.2057A>G)?

GALC p.Ter686= (c.2057A>G) is associated with Krabbe disease (ClinVar).

How common is GALC p.Ter686= (c.2057A>G) in the general population?

GALC p.Ter686= (c.2057A>G) is absent from gnomAD v4.1 (gnomAD).

How is Krabbe disease inherited?

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

GALC p.Ter686=

c.2057A>G · rs970572144 · VCV2078132

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Krabbe disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -4.5
Overall
CADD	0.697	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GALC
Protein: p.Ter686=
Coding: c.2057A>G
MANE Select: NM_000153
dbSNP: rs970572144
Type: single nucleotide variant
Location: chr14:87934733 (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.Ter686Gln Pathogenic/Likely pathogenic ★★ same residue
GALC p.Ter686Tyr 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

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-ter686 (accessed [today's date]).

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