Is GALK1 p.Arg366= (c.1096C>A) pathogenic?

GALK1 p.Arg366= (c.1096C>A) is classified Likely benign in GALK1 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-11-15). Very rare (popmax 0.00224%, eas); Associated with galactokinase deficiency.

What condition is associated with GALK1 p.Arg366= (c.1096C>A)?

GALK1 p.Arg366= (c.1096C>A) is associated with galactokinase deficiency (ClinVar).

How common is GALK1 p.Arg366= (c.1096C>A) in the general population?

GALK1 p.Arg366= (c.1096C>A) is very rare (popmax 0.00224%, eas) (gnomAD).

How is Galactokinase deficiency inherited?

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

GALK1 p.Arg366=

c.1096C>A · rs536478616 · VCV2696170

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Conditions

galactokinase deficiency

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 1.9	phastCons 1
Overall
CADD	5.353	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,606 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000207% 3/1,452,724 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,606
European (non-Finnish)	0.00017%	588,370

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: GALK1
Protein: p.Arg366=
Coding: c.1096C>A
MANE Select: NM_000154
dbSNP: rs536478616
Type: single nucleotide variant
Location: chr17:75758221 (GRCh38)
Gene constraint: LOEUF 1.198 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 97.31 · 20 PDB
Residue 366: an α-helix

Full GALK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

galactokinase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Galactokinase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

GALK1 p.Arg366Trp Uncertain significance ★★ ⚠ same residue
GALK1 p.Arg366Gln Uncertain significance ★ ⚠ same residue
GALK1 p.Arg366Gly Uncertain significance ★ ⚠ same residue
GALK1 p.Arg366Pro Uncertain significance ★ ⚠ same residue
GALK1 p.Arg366fs Likely pathogenic ★ same residue
GALK1 c.355+1G>A Likely pathogenic ★★ same condition
GALK1 c.611+1G>T Pathogenic/Likely pathogenic ★★ same condition
GALK1 c.793+1G>T 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/galk1-p-arg366 (accessed [today's date]).

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