Is AGT p.Arg366Pro (c.1097G>C) pathogenic?

AGT p.Arg366Pro (c.1097G>C) is classified Likely pathogenic in AGT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-17). AlphaMissense: likely pathogenic (0.733); Absent from gnomAD v4.1; Associated with Unexplained young onset end-stage renal disease.

What condition is associated with AGT p.Arg366Pro (c.1097G>C)?

AGT p.Arg366Pro (c.1097G>C) is associated with Unexplained young onset end-stage renal disease (ClinVar).

How common is AGT p.Arg366Pro (c.1097G>C) in the general population?

AGT p.Arg366Pro (c.1097G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGT p.Arg366Pro (c.1097G>C)?

AlphaMissense predicts likely pathogenic (score 0.733) — an in-silico prediction, not a clinical call.

AGT p.Arg366Pro

c.1097G>C · VCV4537511

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.733 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Unexplained young onset end-stage renal disease

Computational evidence

Protein change
AlphaMissense	0.733	likely pathogenic ✓ concordant with ClinVar · top 6% in AGT
REVEL	0.758	pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Pangolin	Δ0.67	loss · gain 0.02 · SpliceAI below 0.2 · 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 is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R375P vs ClinVar R366P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AGT
Protein: p.Arg366Pro
Coding: c.1097G>C
MANE Select: NM_001384479
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

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

Disease context

Unexplained young onset end-stage renal disease

Similar variants

AGT p.Arg366Leu Uncertain significance ★★ ⚠ same residue
AGT p.Arg366Trp Uncertain significance ★★ ⚠ same residue
AGT p.Arg26Trp Conflicting classifications of pathogenicity ★ same condition
AGT p.Ile108Arg Uncertain significance ★ same condition
AGT p.Thr128= Likely benign same condition
AGT c.1060C>T Pathogenic/Likely pathogenic ★★ same type
AGT c.829+1G>T Pathogenic/Likely pathogenic ★★ same type
AGT c.1195G>A 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/agt-p-arg366pro (accessed [today's date]).

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