PLG p.Ser300=
c.900T>C · rs929227724 · VCV2969594
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00695%, nfe)
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 -4.3 | GERP -2.9 |
| Overall | ||
| CADD | 4.43 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00695%
European (non-Finnish) · 82/1,179,762 alleles
Filtering AF
0.00571%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00525%
Overall
0.00539%
87/1,613,680 alleles · very rare
exomes 84/1,461,604 · genomes 3/152,076 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00695% | 14,387 |
| East Asian | 0.00668% | 14,961 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,242 |
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.Ser300=
- Coding
- c.900T>C
- MANE Select
- NM_000301
- dbSNP
- rs929227724
- Type
- single nucleotide variant
- Location
- chr6:160718406 (GRCh38)
- Gene constraint
- LOEUF 0.559 · pLI 0.17 (gnomAD)
- Structure
- AlphaFold pLDDT 83.53 · 49 PDB
- Residue 300
- the kringle 3 domain
Similar variants
- 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
- PLG p.Ala507Val 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-ser300 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown