AASS p.Pro331=
c.993G>A · rs752693651 · VCV734710
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0516%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.23 | donor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.3 | GERP -3.4 |
| Overall | ||
| CADD | 12.33 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0516%
South Asian · 47/91,070 alleles
Filtering AF
0.0399%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0357%
Overall
0.00496%
80/1,613,866 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0516% | 1,938 |
| Admixed American | 0.0133% | 7,497 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,927 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
| African / African-American | 0.00267% | 37,427 |
| Finnishnot grpmax-eligible | 0.00156% | 63,994 |
| European (non-Finnish) | 0.00119% | 84,287 |
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.Pro331=
- Coding
- c.993G>A
- MANE Select
- NM_005763
- dbSNP
- rs752693651
- Type
- single nucleotide variant
- Location
- chr7:122115124 (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 331
- the 'lysine-ketoglutarate reductase' region
Similar variants
- AASS p.Pro331Leu Benign ★ ⚠ same residue
- 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
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-pro331 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown