PLG p.Asp238=
c.714T>C · VCV3593308
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
Conditions
2
angioedema, hereditary, 4
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 -6.2 | GERP -3.8 |
| Overall | ||
| CADD | 0.297 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000434%
7/1,613,512 alleles · ultra-rare
exomes 6/1,461,344 · genomes 1/152,168 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,229 |
| South Asian | 0.0011% | 91,070 |
| European (non-Finnish) | 0.000254% | 393,188 |
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
- PLG
- Protein
- p.Asp238=
- Coding
- c.714T>C
- MANE Select
- NM_000301
- Type
- single nucleotide variant
- Location
- chr6:160716690 (GRCh38)
- Gene constraint
- LOEUF 0.559 · pLI 0.17 (gnomAD)
- Structure
- AlphaFold pLDDT 83.53 · 49 PDB
- Residue 238
- a β-strand; the kringle 2 domain
Similar variants
- PLG p.Lys330Glu Pathogenic ★★ ⚠ same condition
- PLG p.Lys38Glu Pathogenic/Likely pathogenic ★★ ⚠ same condition
- PLG c.669-3C>G Uncertain significance ★★ same condition
- PLG p.Ala216Thr Uncertain significance ★★ ⚠ same condition
- PLG p.Ala494Glu Uncertain significance ★★ ⚠ same condition
- PLG p.Ala507Val Uncertain significance ★★ ⚠ same condition
- PLG p.Ala675Val Uncertain significance ★★ ⚠ same condition
- PLG p.Arg172Gly Uncertain significance ★★ ⚠ same condition
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/plg-p-asp238 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown