PLG p.Pro139=
c.417T>C · rs374989402 · VCV3021589
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. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.4 | GERP -3.8 |
| Overall | ||
| CADD | 1.43 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0187%
African / African-American · 14/74,954 alleles
Filtering AF
0.0112%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00904%
Overall
0.00112%
18/1,610,558 alleles · ultra-rare
exomes 7/1,458,270 · genomes 11/152,288 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0187% | 5,354 |
| Admixed American | 0.00667% | 15,003 |
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.Pro139=
- Coding
- c.417T>C
- MANE Select
- NM_000301
- dbSNP
- rs374989402
- Type
- single nucleotide variant
- Location
- chr6:160712995 (GRCh38)
- Gene constraint
- LOEUF 0.559 · pLI 0.17 (gnomAD)
- Structure
- AlphaFold pLDDT 83.53 · 49 PDB
- Residue 139
- the 'disordered' region; the kringle 1 domain; a turn
Similar variants
- PLG p.Pro139Thr Uncertain significance ★ ⚠ same residue
- PLG p.Pro139_Thr141del Uncertain significance ★★ same residue
- PLG p.Lys330Glu Pathogenic ★★ ⚠ same type
- PLG p.Lys38Glu Pathogenic/Likely pathogenic ★★ ⚠ same type
- PLG c.2271+5G>A Uncertain significance ★★ same type
- PLG c.669-3C>G Uncertain significance ★★ same type
- PLG p.Ala216Thr Uncertain significance ★★ ⚠ same type
- PLG p.Ala459Val 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/plg-p-pro139 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown