GALT p.Asp90=
c.270T>C · rs1300102277 · VCV913656
ClinGen expert panel — Galactosemia VCEP
Uncertain Significance for galactosemia. Applied ACMG criteria (verbatim):
PM2_Supporting PP3
Curation rationale (ClinGen, verbatim)
The c.291C>T variant is a synonymous (silent) variant that the computational splicing predictor SpliceAI gives a delta score of 0.2 for acceptor gain; however, the acceptor gain prediction is the canonical acceptor (PP3). The filtering allele frequency of the c.270T>C variant in GALT is 0.00006614 for Admixed American chromosomes by gnomAD v4.1.1, which is lower than the ClinGen Galactosemia threshold (≤ 0.0005) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting). In summary, this variant meets the criteria to be classified as variant of uncertain significance for galactosemia based on the ACMG/AMP criteria applied, as specified by the ClinGen Galactosemia VCEP: PM2_Supporting, PP3
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.20 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.21 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -3.8 | GERP -3.4 |
| Overall | ||
| CADD | 0.538 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,042 |
| Admixed American | 0.0133% | 7,501 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,241 |
| European (non-Finnish) | 0.000678% | 147,503 |
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
- GALT
- Protein
- p.Asp90=
- Coding
- c.270T>C
- MANE Select
- NM_000155
- dbSNP
- rs1300102277
- Type
- single nucleotide variant
- Location
- chr9:34647509 (GRCh38)
- Gene constraint
- LOEUF 0.935 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 92.08 · 2 PDB
Disease context
classic galactosemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Classic galactosemia (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
- Prevalence
- 1-9 / 100 000 (Europe)
Similar variants
- GALT p.Asp90His Uncertain significance ★ ⚠ same residue
- GALT c.1060-1G>A Pathogenic/Likely pathogenic ★★ same condition
- GALT c.252+1G>A Pathogenic ★★ same condition
- GALT c.253-1G>A Pathogenic/Likely pathogenic ★★ same condition
- GALT c.253-2A>G Pathogenic ★★ same condition
- GALT c.328+2T>G Pathogenic/Likely pathogenic ★★ same condition
- GALT c.329-2A>C Pathogenic ★★ same condition
- GALT c.377+1G>A 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/galt-p-asp90 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown