ALAD p.Ile260=
c.780C>A · rs374069780 · VCV1512096
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0111%, 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 -2.7 | GERP -3.9 |
| Overall | ||
| CADD | 1.26 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0111%
European (non-Finnish) · 131/1,180,036 alleles
Filtering AF
0.00952%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00896%
Overall
0.00855%
138/1,613,656 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0111% | 9,008 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,614 |
| African / African-American | 0.004% | 24,970 |
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.Ile260=
- Coding
- c.780C>A
- MANE Select
- NM_000031
- dbSNP
- rs374069780
- Type
- single nucleotide variant
- Location
- chr9:113389459 (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 260
- an α-helix
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-ile260 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown