PLAA p.Ala289=
c.867G>A · rs1352823433 · VCV1597777
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.31 | donor loss, 9 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.6 | GERP -2.2 |
| Overall | ||
| CADD | 11.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/59,978 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000682%
11/1,613,678 alleles · very rare
exomes 7/1,461,438 · genomes 4/152,240 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 19,993 |
| South Asian | 0.00329% | 30,349 |
| East Asian | 0.00223% | 44,856 |
| European (non-Finnish) | 0.000339% | 294,934 |
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
- PLAA
- Protein
- p.Ala289=
- Coding
- c.867G>A
- MANE Select
- NM_001031689
- dbSNP
- rs1352823433
- Type
- single nucleotide variant
- Location
- chr9:26925827 (GRCh38)
- Gene constraint
- LOEUF 0.678 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.87 · 5 PDB
Similar variants
- PLAA p.Arg524Ter Likely pathogenic ★★ same type
- PLAA p.Ala156Val Uncertain significance ★★ ⚠ same type
- PLAA p.Ala264Thr Uncertain significance ★★ ⚠ same type
- PLAA p.Ala271Val Uncertain significance ★★ ⚠ same type
- PLAA p.Arg268Gln Uncertain significance ★★ ⚠ same type
- PLAA p.Arg373Thr Uncertain significance ★★ ⚠ same type
- PLAA p.Arg499Cys Uncertain significance ★★ same type
- PLAA p.Arg7Ser 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/plaa-p-ala289 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown