ALAD p.Val251=
c.753G>A · VCV3686116
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
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 0.43 | GERP -3.9, phastCons 0.99 |
| Overall | ||
| CADD | 10.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,046 alleles
Overall
6.84e-05%
1/1,461,772 alleles · very rare
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
- ALAD
- Protein
- p.Val251=
- Coding
- c.753G>A
- MANE Select
- NM_000031
- Type
- single nucleotide variant
- Location
- chr9:113389486 (GRCh38)
- Gene constraint
- LOEUF 0.63 · pLI 0.10 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 96.34 · 4 PDB
- Residue 251
- a β-strand
Similar variants
- ALAD p.Gly133Arg Likely pathogenic ★★ same type
- ALAD c.*127C>T Uncertain significance ★★ same type
- ALAD c.*363G>A Uncertain significance ★★ same type
- ALAD p.Ala93Thr Uncertain significance ★★ ⚠ same type
- ALAD p.Arg147Cys Uncertain significance ★★ ⚠ same type
- ALAD p.Arg174His Uncertain significance ★★ ⚠ same type
- ALAD p.Arg17Gln Uncertain significance ★★ ⚠ same type
- ALAD p.Arg222Cys Uncertain significance ★★ ⚠ 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/alad-p-val251 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown