Is PLG p.Thr697= (c.2091C>T) pathogenic?

PLG p.Thr697= (c.2091C>T) is classified Likely benign in PLG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). Rare (popmax 0.105%, amr).

How common is PLG p.Thr697= (c.2091C>T) in the general population?

PLG p.Thr697= (c.2091C>T) is rare (popmax 0.105%, amr) (gnomAD).

PLG p.Thr697=

c.2091C>T · rs755323263 · VCV2696425

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.105%, 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 -8.6	GERP -3.4
Overall
CADD	0.066	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.105% Admixed American · 63/59,998 alleles

Filtering AF 0.0842% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0766%

Overall 0.00645% 104/1,612,844 alleles · rare exomes 99/1,460,638 · genomes 5/152,206 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.105%	952
East Asian	0.0356%	2,805
African / African-American	0.004%	24,975
Remaining individualsnot grpmax-eligible	0.0032%	31,224
European (non-Finnish)	0.0017%	58,945

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.Thr697=
Coding: c.2091C>T
MANE Select: NM_000301
dbSNP: rs755323263
Type: single nucleotide variant
Location: chr6:160741383 (GRCh38)
Gene constraint: LOEUF 0.559 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 83.53 · 49 PDB
Residue 697: the peptidase s1 domain

Full PLG gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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-thr697 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown