AASS p.Pro404=
c.1212G>T · VCV3623663
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000169%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.32 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -9.7 | GERP -2.9 |
| Overall | ||
| CADD | 9.491 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000169%
European (non-Finnish) · 2/1,179,970 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000124%
2/1,614,022 alleles · very rare
exomes 2/1,461,766 · genomes 0/152,256 · joint denominator
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.Pro404=
- Coding
- c.1212G>T
- MANE Select
- NM_005763
- Type
- single nucleotide variant
- Location
- chr7:122113184 (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 404
- the 'lysine-ketoglutarate reductase' region; an α-helix
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-pro404 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown