A4GALT p.Pro46=
c.138C>G · VCV4948289
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00171%, amr)
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 -0.09 | |
| Overall | ||
| CADD | 4.615 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00171%
Admixed American · 1/58,546 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000311%
5/1,605,362 alleles · very rare
exomes 5/1,453,126 · genomes 0/152,236 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00171% | 58,546 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,212 |
| European (non-Finnish) | 0.000255% | 392,069 |
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
- A4GALT
- Protein
- p.Pro46=
- Coding
- c.138C>G
- MANE Select
- NM_017436
- Type
- single nucleotide variant
- Location
- chr22:42693814 (GRCh38)
- Gene constraint
- LOEUF 1.393 · pLI 0.08 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.54
Similar variants
- A4GALT p.Arg10Trp Uncertain significance ★★ ⚠ same type
- A4GALT p.Arg151Trp Uncertain significance ★★ ⚠ same type
- A4GALT p.Gly14Asp Uncertain significance ★★ ⚠ same type
- A4GALT p.Pro137Ser Uncertain significance ★★ ⚠ same type
- A4GALT p.Pro251Leu Uncertain significance ★★ ⚠ same type
- A4GALT p.Thr324Met Uncertain significance ★★ ⚠ same type
- A4GALT p.Val42Ala Uncertain significance ★★ ⚠ same type
- A4GALT p.Gln163Arg Benign ★★ 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/a4galt-p-pro46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown