| Variant name/designation | Nucleotide change | Amino acid change | Frequency / population | Effect on enzyme activity | Clinical phenotype / severity |
|---|---|---|---|---|---|
| Q188R | c.563A>G | p.Gln188Arg (Q188R) | Most common pathogenic GALT variant in Caucasian/European populations; ~60–70% of mutant alleles/cases in cited reports (pqac-00000009, pqac-00000010, pqac-00000015) | Near-complete to undetectable GALT activity when homozygous; severe catalytic defect, with major loss of function (pqac-00000009, pqac-00000010, pqac-00000015) | Classic galactosemia; usually severe neonatal disease and poor prognosis when untreated (pqac-00000010, pqac-00000011) |
| K285N | c.855G>T | p.Lys285Asn (K285N) | Second most common pathogenic variant in Europeans; ~26–34% of galactosemia alleles in cited review (pqac-00000016) | Causes major loss of function; ~50% activity loss in heterozygotes and complete loss in homozygotes (pqac-00000016) | Severe/classic galactosemia phenotype; consistently associated with severe disease (pqac-00000010, pqac-00000011, pqac-00000016) |
| Duarte D2 | often defined by c.940A>G in cis with promoter deletion c.-119_-116delGTCA and additional linked changes | p.Asn314Asp (N314D) | Common biochemical variant; Duarte allele prevalence ~5–6% in North American non-galactosemic populations and ~2% in Japan; enzyme activity often ~50% in RBCs (pqac-00000012, pqac-00000014, pqac-00000015) | Reduced but residual activity; decreased RBC GALT activity attributed to reduced abundance/instability rather than N314D alone (pqac-00000012, pqac-00000015) | Generally clinically benign/asymptomatic as a standalone Duarte variant; Duarte galactosemia occurs when paired with a classic pathogenic allele (pqac-00000009, pqac-00000012, pqac-00000014) |
| D1 / Los Angeles | c.940A>G in cis with c.652C>T (linked synonymous change in cited review) | p.Asn314Asp (N314D) | Described biochemical variant found globally; less emphasized than D2 but recognized in classic mutation reviews (pqac-00000010, pqac-00000016) | Associated with normal or increased erythrocyte GALT activity, likely via increased protein abundance/overexpression rather than intrinsic catalytic enhancement (pqac-00000010, pqac-00000011, pqac-00000016) | Not pathogenic by itself; considered a benign/high-activity biochemical variant (pqac-00000010, pqac-00000011) |
| S135L | not specified in gathered evidence | p.Ser135Leu (S135L) | Reported variant in classic mutation review; population frequency not specified in gathered evidence (pqac-00000010) | Tissue-specific residual activity reported; individuals carrying S135L appear to retain GALT activity in some tissues (pqac-00000010) | Often associated with galactosemia but may show atypical or somewhat milder biochemical behavior because of tissue-specific residual activity (pqac-00000010) |


*Table: This table summarizes major disease-causing and biochemical GALT variants relevant to classic galactosemia, including their frequencies, effects on enzyme activity, and associated clinical severity. It is useful for linking genotype to functional impact during annotation and interpretation.*