Is GALE p.Ser48= (c.144C>T) pathogenic?

GALE p.Ser48= (c.144C>T) is classified Likely benign in GALE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-02-18). Very rare (popmax 0.00667%, amr); Associated with galactose epimerase deficiency.

What condition is associated with GALE p.Ser48= (c.144C>T)?

GALE p.Ser48= (c.144C>T) is associated with galactose epimerase deficiency (ClinVar).

How common is GALE p.Ser48= (c.144C>T) in the general population?

GALE p.Ser48= (c.144C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

How is Galactose epimerase deficiency inherited?

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

GALE p.Ser48=

c.144C>T · rs1304532208 · VCV2720739

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Conditions

galactose epimerase 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 4.6	GERP 0.34, phastCons 1
Overall
CADD	10.79	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/59,986 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000806% 13/1,613,870 alleles · very rare exomes 12/1,461,706 · genomes 1/152,164 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,997
European (non-Finnish)	0.000763%	131,100

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: GALE
Protein: p.Ser48=
Coding: c.144C>T
MANE Select: NM_001008216
dbSNP: rs1304532208
Type: single nucleotide variant
Location: chr1:23798708 (GRCh38)
Gene constraint: LOEUF 0.925 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.22 · 11 PDB
Residue 48: an α-helix

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

Disease context

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

For Galactose epimerase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

GALE p.Ser48fs Pathogenic/Likely pathogenic ★★ same residue
GALE c.351+1G>T Likely pathogenic ★★ same condition
GALE c.642+1G>A Likely pathogenic ★★ same condition
GALE c.643-2A>C Likely pathogenic ★★ same condition
GALE c.796-1G>T Pathogenic/Likely pathogenic ★★ same condition
GALE p.Arg169Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
GALE p.Arg239Trp Pathogenic/Likely pathogenic ★★ same condition
GALE p.Arg335His 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/gale-p-ser48 (accessed [today's date]).

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