PLG p.Cys176=
c.528C>T · rs558599800 · VCV1960685
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0517%, amr)
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 -8 | GERP -3.8 |
| Overall | ||
| CADD | 1.838 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0517%
Admixed American · 31/59,998 alleles
Filtering AF
0.0374%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0325%
Overall
0.00398%
64/1,610,016 alleles · ultra-rare
exomes 42/1,457,826 · genomes 22/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0517% | 1,935 |
| East Asian | 0.00891% | 11,218 |
| African / African-American | 0.00801% | 12,482 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,132 |
| European (non-Finnish) | 0.0017% | 58,906 |
| South Asian | 0.0011% | 90,946 |
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.Cys176=
- Coding
- c.528C>T
- MANE Select
- NM_000301
- dbSNP
- rs558599800
- Type
- single nucleotide variant
- Location
- chr6:160713106 (GRCh38)
- Gene constraint
- LOEUF 0.559 · pLI 0.17 (gnomAD)
- Structure
- AlphaFold pLDDT 83.53 · 49 PDB
- Residue 176
- a disulfide bond; the kringle 1 domain
Similar variants
- PLG p.Cys176Ter Pathogenic ★ 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
- PLG p.Ala494Glu 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-cys176 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown