PLG p.Ala694=
c.2082T>C · rs4252170 · VCV1268733
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 11.1%, eas) — too common for a highly-penetrant pathogenic allele
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 -9.5 | GERP -3.4 |
| Overall | ||
| CADD | 0.098 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
11.1%
East Asian · 4,987/44,858 alleles
Filtering AF
10.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 10.8%
Overall
7.71%
124,238/1,612,254 alleles · common
exomes 114,579/1,459,896 · genomes 9,659/152,358 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 11.1% | 9 |
| Finnishnot grpmax-eligible | 9.83% | 10 |
| Middle Eastern | 9.66% | 10 |
| Ashkenazi Jewishnot grpmax-eligible | 8.52% | 12 |
| Remaining individualsnot grpmax-eligible | 8.26% | 12 |
| European (non-Finnish) | 8.06% | 12 |
| Admixed American | 5.96% | 17 |
| Amishnot grpmax-eligible | 5.81% | 17 |
| South Asian | 5.18% | 19 |
| African / African-American | 1.85% | 54 |
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.Ala694=
- Coding
- c.2082T>C
- MANE Select
- NM_000301
- dbSNP
- rs4252170
- Type
- single nucleotide variant
- Location
- chr6:160741374 (GRCh38)
- Gene constraint
- LOEUF 0.559 · pLI 0.17 (gnomAD)
- Structure
- AlphaFold pLDDT 83.53 · 49 PDB
- Residue 694
- the peptidase s1 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-ala694 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown