Is GALE p.Asp332= (c.996T>C) pathogenic?

GALE p.Asp332= (c.996T>C) is classified Likely benign in GALE (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-25). Ultra-rare (popmax 0.0164%, mid); Associated with galactose epimerase deficiency.

What condition is associated with GALE p.Asp332= (c.996T>C)?

GALE p.Asp332= (c.996T>C) is associated with galactose epimerase deficiency (ClinVar).

How common is GALE p.Asp332= (c.996T>C) in the general population?

GALE p.Asp332= (c.996T>C) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Galactose epimerase deficiency inherited?

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

GALE p.Asp332=

c.996T>C · rs746112570 · VCV2909583

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 0.2	GERP -2.7, phastCons 0.29
Overall
CADD	3.156	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00175%

Overall 0.00211% 34/1,613,896 alleles · ultra-rare exomes 32/1,461,710 · genomes 2/152,186 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.0028%	35,758

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.Asp332=
Coding: c.996T>C
MANE Select: NM_001008216
dbSNP: rs746112570
Type: single nucleotide variant
Location: chr1:23796000 (GRCh38)
Gene constraint: LOEUF 0.925 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.22 · 11 PDB
Residue 332: 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 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
GALE p.Gly302Asp 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-asp332 (accessed [today's date]).

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