AASS p.Leu499=
c.1497A>G · rs369170463 · VCV771874
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0832%, mid)
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 0.59 | GERP 0.071, phastCons 1 |
| Overall | ||
| CADD | 6.696 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0832%
Middle Eastern · 5/6,008 alleles
Filtering AF
0.0327%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0213%
Overall
0.00499%
80/1,602,422 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0832% | 1,202 |
| South Asian | 0.0334% | 2,994 |
| Remaining individualsnot grpmax-eligible | 0.00967% | 10,343 |
| European (non-Finnish) | 0.00323% | 30,939 |
| African / African-American | 0.00137% | 72,938 |
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
- AASS
- Protein
- p.Leu499=
- Coding
- c.1497A>G
- MANE Select
- NM_005763
- dbSNP
- rs369170463
- Type
- single nucleotide variant
- Location
- chr7:122098776 (GRCh38)
- Gene constraint
- LOEUF 0.948 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 90.73 · 9 PDB
- Residue 499
- an α-helix; the 'saccharopine dehydrogenase' region
Similar variants
- AASS c.1767-1G>A Pathogenic/Likely pathogenic ★★ same type
- AASS p.Arg132His Likely pathogenic ★★ same type
- AASS p.Arg132Cys Uncertain significance ★★ ⚠ same type
- AASS p.Arg146Trp Uncertain significance ★★ ⚠ same type
- AASS p.Asn34Lys Uncertain significance ★★ ⚠ same type
- AASS p.Asn865Ser Uncertain significance ★★ ⚠ same type
- AASS p.Gln921Arg Uncertain significance ★★ ⚠ same type
- AASS p.Gly167Cys 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/aass-p-leu499 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown