PLG p.Arg696=
c.2086C>A · rs144869703 · VCV3233501
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000594%, 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 1.5 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 4.416 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000594%
European (non-Finnish) · 7/1,179,110 alleles
Filtering AF
0.000247%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000159%
Overall
0.000434%
7/1,613,060 alleles · very rare
exomes 5/1,460,838 · genomes 2/152,222 · joint denominator
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.Arg696=
- Coding
- c.2086C>A
- MANE Select
- NM_000301
- dbSNP
- rs144869703
- Type
- single nucleotide variant
- Location
- chr6:160741378 (GRCh38)
- Gene constraint
- LOEUF 0.559 · pLI 0.17 (gnomAD)
- Structure
- AlphaFold pLDDT 83.53 · 49 PDB
- Residue 696
- the peptidase s1 domain
Similar variants
- PLG p.Arg696Gln Likely benign ★★ same residue
- PLG p.Arg696Gly Uncertain significance ★ ⚠ same residue
- PLG p.Arg696Trp 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
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-arg696 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown