Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0364%, nfe)
Conditions
1
Inborn genetic diseases
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 2.5 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 2.409 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0364%
European (non-Finnish) · 429/1,179,616 alleles
Filtering AF
0.0335%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0323%
Overall
0.0287%
462/1,609,862 alleles · ultra-rare
exomes 421/1,457,592 · genomes 41/152,270 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0364% | 2,750 |
| Remaining individualsnot grpmax-eligible | 0.0209% | 4,791 |
| Admixed American | 0.0184% | 5,446 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,799 |
| African / African-American | 0.00667% | 14,983 |
| Finnishnot grpmax-eligible | 0.00318% | 31,458 |
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.Lys4=
- Coding
- c.12G>A
- MANE Select
- NM_000301
- dbSNP
- rs4252061
- Type
- single nucleotide variant
- Location
- chr6:160702316 (GRCh38)
- Gene constraint
- LOEUF 0.559 · pLI 0.17 (gnomAD)
- Structure
- AlphaFold pLDDT 83.53 · 49 PDB
Similar variants
- PLG p.Ala459Val Uncertain significance ★★ ⚠ same condition
- PLG p.Ala77Thr Uncertain significance ★★ ⚠ same condition
- PLG p.Arg253Cys Uncertain significance ★★ ⚠ same condition
- PLG p.Arg343Gln Uncertain significance ★★ ⚠ same condition
- PLG p.Arg656Trp Uncertain significance ★★ ⚠ same condition
- PLG p.Asn690Asp Uncertain significance ★★ ⚠ same condition
- PLG p.Asp177Asn Uncertain significance ★★ ⚠ same condition
- PLG p.Asp430Glu 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-lys4 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown