Is AGT p.Arg366Leu (c.1097G>T) pathogenic?

AGT p.Arg366Leu (c.1097G>T) is classified Uncertain significance in AGT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-09). AlphaMissense: likely benign (0.3052); Very rare (popmax 0.00119%, nfe); Associated with renal tubular dysgenesis of genetic origin.

What condition is associated with AGT p.Arg366Leu (c.1097G>T)?

AGT p.Arg366Leu (c.1097G>T) is associated with renal tubular dysgenesis of genetic origin (ClinVar).

How common is AGT p.Arg366Leu (c.1097G>T) in the general population?

AGT p.Arg366Leu (c.1097G>T) is very rare (popmax 0.00119%, nfe) (gnomAD).

What do computational predictors say about AGT p.Arg366Leu (c.1097G>T)?

AlphaMissense predicts likely benign (score 0.3052) — an in-silico prediction, not a clinical call.

AGT p.Arg366Leu

c.1097G>T · rs74315283 · VCV1440909

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3052 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

renal tubular dysgenesis of genetic origin

Computational evidence

Protein change
AlphaMissense	0.3052	likely benign
REVEL	0.729	pathogenic-leaning
⇒ REVEL calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.68	loss · gain 0.02 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 3.7	GERP 1.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 7,679 bp · p 0.88 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R375L vs ClinVar R366L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% European (non-Finnish) · 14/1,179,984 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000867% 14/1,613,874 alleles · very rare

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: AGT
Protein: p.Arg366Leu
Coding: c.1097G>T
MANE Select: NM_001384479
dbSNP: rs74315283
Type: single nucleotide variant
Location: chr1:230705933 (GRCh38)
Gene constraint: LOEUF 1.202 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.74 · 22 PDB
Residue 366: a UniProt-annotated variant site (in rtd); a β-strand

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

Disease context

renal tubular dysgenesis of genetic origin — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AGT p.Arg366Trp Uncertain significance ★★ ⚠ same residue
AGT p.Arg366Pro Likely pathogenic ★ same residue
AGT c.1060C>T Pathogenic/Likely pathogenic ★★ same condition
AGT c.829+1G>T Pathogenic/Likely pathogenic ★★ same condition
AGT c.1195G>A Uncertain significance ★★ ⚠ same condition
AGT c.856G>T Uncertain significance ★★ ⚠ same condition
AGT c.862C>T Uncertain significance ★★ ⚠ same condition
AGT c.-17G>C 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/agt-p-arg366leu (accessed [today's date]).

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