Is GALK1 p.Pro67= (c.201C>T) pathogenic?

GALK1 p.Pro67= (c.201C>T) is classified Likely benign in GALK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-16). Very rare (popmax 0.00017%, nfe); Associated with galactokinase deficiency.

What condition is associated with GALK1 p.Pro67= (c.201C>T)?

GALK1 p.Pro67= (c.201C>T) is associated with galactokinase deficiency (ClinVar).

How common is GALK1 p.Pro67= (c.201C>T) in the general population?

GALK1 p.Pro67= (c.201C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

How is Galactokinase deficiency inherited?

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

GALK1 p.Pro67=

c.201C>T · VCV3703748

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

galactokinase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.49	phastCons 0.99
Overall
CADD	6.238	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,173,546 alleles

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

Overall 0.000188% 3/1,596,230 alleles · very rare exomes 3/1,443,928 · genomes 0/152,302 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00162%	61,830
European (non-Finnish)grpmax	0.00017%	586,772

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro67=
Coding: c.201C>T
MANE Select: NM_000154
Type: single nucleotide variant
Location: chr17:75764051 (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 67: a β-strand

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 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
GALK1 c.793+2T>C Pathogenic/Likely pathogenic ★★ same condition
GALK1 c.793+2T>G Pathogenic/Likely pathogenic ★★ same condition
GALK1 p.Arg256Trp Pathogenic/Likely pathogenic ★★ same condition
GALK1 p.Arg301Ter Pathogenic/Likely pathogenic ★★ same condition
GALK1 p.Cys170Ter 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-pro67 (accessed [today's date]).

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