AAAS p.Ala253=
c.759C>T · rs751836874 · VCV2820773
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0245%, eas)
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 0.87 | GERP -4, phastCons 1 |
| Overall | ||
| CADD | 9.484 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0245%
East Asian · 11/44,876 alleles
Filtering AF
0.0137%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0106%
Overall
0.000753%
11/1,461,214 alleles · ultra-rare
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
- AAAS
- Protein
- p.Ala253=
- Coding
- c.759C>T
- MANE Select
- NM_015665
- dbSNP
- rs751836874
- Type
- single nucleotide variant
- Location
- chr12:53309652 (GRCh38)
- Gene constraint
- LOEUF 0.921 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.45 · 2 PDB
- Residue 253
- a UniProt-annotated variant site (in aaas)
Similar variants
- AAAS p.Ala253Thr Uncertain significance ★ ⚠ same residue
- AAAS c.1331+1G>A Pathogenic ★★ same type
- AAAS c.1331+1G>C Pathogenic/Likely pathogenic ★★ same type
- AAAS c.446+1G>A Pathogenic ★★ same type
- AAAS c.446+1G>T Pathogenic/Likely pathogenic ★★ same type
- AAAS c.810+1G>A Pathogenic/Likely pathogenic ★★ same type
- AAAS c.936-1G>C Pathogenic/Likely pathogenic ★★ same type
- AAAS p.Ala167Glu Pathogenic/Likely pathogenic ★★ 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/aaas-p-ala253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown