GALT p.Val233=
c.699C>A · rs111033756 · VCV3639687
ClinGen expert panel — Galactosemia VCEP
Likely Benign for galactosemia. Applied ACMG criteria (verbatim):
PM2_Supporting BP7 BP4
Curation rationale (ClinGen, verbatim)
The c.699C>A (p.Val233=) variant (NM_000155.4) is a synonymous (silent) variant that is not predicted by SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not predicted to be involved in splicing and the codon usage is not predicted to be significantly different (BP4, BP7). The c.699C>A variant in GALT is not found in gnomAD v4.1.0, which is lower than the ClinGen Galactosemia threshold (≤0.0005) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting). To our knowledge, this variant is not reported in the clinical literature in an affected individual. The Galactosemia VCEP does not consider PM2_Supporting as conflicting data with BP4 and BP7. Therefore, this variant meets the criteria to be classified as likely benign for galactosemia. ACMG/AMP criteria applied, as specified by the ClinGen Galactosemia VCEP: PM2_Supporting, BP4, BP7 (GALT specifications v1.0.0).
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 carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.21 | GERP -1.6, phastCons 0.25 |
| Overall | ||
| CADD | 6.111 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- GALT
- Protein
- p.Val233=
- Coding
- c.699C>A
- MANE Select
- NM_000155
- dbSNP
- rs111033756
- Type
- single nucleotide variant
- Location
- chr9:34648773 (GRCh38)
- Gene constraint
- LOEUF 0.935 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 92.08 · 2 PDB
- Residue 233
- a β-strand
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.Val233Phe 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-val233 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown