PLAA p.Ala512=
c.1536C>T · rs370264645 · VCV2892808
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.164%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.136 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.4 | GERP -0.87, phastCons 1 |
| Overall | ||
| CADD | 8.879 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.164%
Middle Eastern · 10/6,080 alleles
Filtering AF
0.0891%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0679%
Overall
0.00646%
104/1,611,098 alleles · rare
exomes 93/1,459,084 · genomes 11/152,014 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.164% | 608 |
| African / African-American | 0.012% | 8,312 |
| Remaining individualsnot grpmax-eligible | 0.00801% | 12,477 |
| East Asian | 0.00669% | 14,955 |
| European (non-Finnish) | 0.00654% | 15,294 |
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.Ala512=
- Coding
- c.1536C>T
- MANE Select
- NM_001031689
- dbSNP
- rs370264645
- Type
- single nucleotide variant
- Location
- chr9:26913898 (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-ala512 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown