PLVAP p.Arg423=
c.1269G>A · rs746069692 · VCV1978624
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.115%, 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 |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.6 | GERP -1, phastCons 0.84 |
| Overall | ||
| CADD | 5.968 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.115%
South Asian · 105/91,040 alleles
Filtering AF
0.0974%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0907%
Overall
0.00713%
115/1,613,668 alleles · rare
exomes 113/1,461,366 · genomes 2/152,302 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.115% | 867 |
| Middle Eastern | 0.0497% | 2,013 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,412 |
| European (non-Finnish) | 8.48e-05% | 1,179,759 |
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
- PLVAP
- Protein
- p.Arg423=
- Coding
- c.1269G>A
- MANE Select
- NM_031310
- dbSNP
- rs746069692
- Type
- single nucleotide variant
- Location
- chr19:17360581 (GRCh38)
- Gene constraint
- LOEUF 1.015 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.39
- Residue 423
- a UniProt-annotated variant site (in diar10); a UniProt-annotated variant site (in diar10; the protein is not expressed in the patient biopsy tissues)
Similar variants
- PLVAP p.Arg358Ter Pathogenic ★★ same type
- PLVAP p.Ala292Val Uncertain significance ★★ ⚠ same type
- PLVAP p.Ala385Thr Uncertain significance ★★ ⚠ same type
- PLVAP p.Ala94Thr Uncertain significance ★★ ⚠ same type
- PLVAP p.Arg13Trp Uncertain significance ★★ ⚠ same type
- PLVAP p.Arg211Cys Uncertain significance ★★ ⚠ same type
- PLVAP p.Arg238His Uncertain significance ★★ ⚠ same type
- PLVAP p.Arg269Cys 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/plvap-p-arg423 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown