AASS p.Ser681=
c.2043C>T · VCV4802240
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0685%, 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 1.9 | GERP 0.87, phastCons 1 |
| Overall | ||
| CADD | 6.333 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0685%
Admixed American · 41/59,860 alleles
Filtering AF
0.0519%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.046%
Overall
0.00301%
44/1,461,248 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0685% | 1,460 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,235 |
| European (non-Finnish) | 8.48e-05% | 1,179,756 |
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.Ser681=
- Coding
- c.2043C>T
- MANE Select
- NM_005763
- Type
- single nucleotide variant
- Location
- chr7:122086153 (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 681
- 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-ser681 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown