PLAT p.Pro543=
c.1629G>A · rs141151565 · VCV712061
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.167%, sas)
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 |
|---|---|---|
| Pangolin | Δ0.29 | gain · loss 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP -14 | GERP -3.8 |
| Overall | ||
| CADD | 0.12 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.167%
South Asian · 152/91,076 alleles
Filtering AF
0.145%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.137%
Overall
0.112%
1,805/1,614,018 alleles · rare
exomes 1,662/1,461,768 · genomes 143/152,250 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.167% | 599 |
| Middle Eastern | 0.132% | 758 |
| European (non-Finnish) | 0.12% | 831 |
| Ashkenazi Jewishnot grpmax-eligible | 0.115% | 871 |
| Remaining individualsnot grpmax-eligible | 0.11% | 906 |
| African / African-American | 0.0706% | 1,415 |
| Finnishnot grpmax-eligible | 0.0531% | 1,883 |
| Admixed American | 0.0517% | 1,936 |
| East Asian | 0.00891% | 11,218 |
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
- PLAT
- Protein
- p.Pro543=
- Coding
- c.1629G>A
- MANE Select
- NM_000930
- dbSNP
- rs141151565
- Type
- single nucleotide variant
- Location
- chr8:42176053 (GRCh38)
- Gene constraint
- LOEUF 0.804 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.28 · 11 PDB
- Residue 543
- the peptidase s1 domain
Similar variants
- PLAT p.Pro543Leu Uncertain significance ★ ⚠ same residue
- PLAT p.Arg184Gly Uncertain significance ★★ ⚠ same type
- PLAT p.Val280Met Uncertain significance ★★ ⚠ same type
- PLAT p.Ala34Asp Likely benign ★★ same type
- PLAT p.Ala493= Benign/Likely benign ★★ same type
- PLAT p.Arg561Ter Benign ★★ same type
- PLAT p.Ser154= Likely benign ★★ same type
- PLAT p.Ser513= Benign ★★ 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/plat-p-pro543 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown