GALC p.Arg396Pro
c.1187G>C · VCV4689318
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.8711 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.8711 | likely pathogenic |
|---|---|---|
| REVEL | 0.839 | moderately pathogenic-leaning |
| SaProt | LLR -5.16 | tolerated |
| ⇒ AlphaMissense and REVEL call this damaging; SaProt does not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.3, phastCons 1 |
| Regional constraint | o/e 1.03 | unconstrained · MANE · 58 kb · p 0.37 · regional, not allelic |
| Overall | ||
| CADD | 27.7 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
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
- GALC
- Protein
- p.Arg396Pro
- Coding
- c.1187G>C
- MANE Select
- NM_000153
- Type
- single nucleotide variant
- Location
- chr14:87950723 (GRCh38)
- Gene constraint
- LOEUF 1.019 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.56
- Residue 396
- a UniProt-annotated variant site (in krb); a binding site
Similar variants
- GALC p.Arg396Trp Pathogenic ★★ ⚠ same residue
- GALC p.Arg396Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
- GALC p.Arg396= Likely benign ★ same residue
- GALC p.Arg396fs Likely pathogenic ★ same residue
- GALC c.1033+1G>A Likely pathogenic ★★ same type
- GALC c.1034-1G>C Pathogenic/Likely pathogenic ★★ same type
- GALC c.1034-2A>G Pathogenic/Likely pathogenic ★★ same type
- GALC c.1161+2T>A Likely pathogenic ★★ same type
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/galc-p-arg396pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown