PLAA p.Leu552=
c.1654T>C · rs116722627 · VCV2419090
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0187%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.238 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>C here scores Δ0.23 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 1 | GERP 0.21, phastCons 0.94 |
| Overall | ||
| CADD | 7.297 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0187%
African / African-American · 14/74,830 alleles
Filtering AF
0.0112%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00906%
Overall
0.00144%
23/1,601,772 alleles · ultra-rare
exomes 14/1,449,456 · genomes 9/152,316 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0187% | 5,345 |
| East Asian | 0.0112% | 8,937 |
| Admixed American | 0.00167% | 59,986 |
| South Asian | 0.0011% | 90,770 |
| European (non-Finnish) | 0.000171% | 584,559 |
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.Leu552=
- Coding
- c.1654T>C
- MANE Select
- NM_001031689
- dbSNP
- rs116722627
- Type
- single nucleotide variant
- Location
- chr9:26910341 (GRCh38)
- Gene constraint
- LOEUF 0.678 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.87 · 5 PDB
- Residue 552
- an α-helix; the pul domain
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-leu552 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown