Is AGT p.Pro373Ala (c.1117C>G) pathogenic?

AGT p.Pro373Ala (c.1117C>G) is classified Uncertain significance in AGT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-26). AlphaMissense: likely pathogenic (0.7506); Very rare (popmax 0.000847%, nfe); Associated with renal tubular dysgenesis of genetic origin.

What condition is associated with AGT p.Pro373Ala (c.1117C>G)?

AGT p.Pro373Ala (c.1117C>G) is associated with renal tubular dysgenesis of genetic origin (ClinVar).

How common is AGT p.Pro373Ala (c.1117C>G) in the general population?

AGT p.Pro373Ala (c.1117C>G) is very rare (popmax 0.000847%, nfe) (gnomAD).

What do computational predictors say about AGT p.Pro373Ala (c.1117C>G)?

AlphaMissense predicts likely pathogenic (score 0.7506) — an in-silico prediction, not a clinical call.

AGT p.Pro373Ala

c.1117C>G · VCV3580961

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7506 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000847%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

renal tubular dysgenesis of genetic origin

Computational evidence

Protein change
AlphaMissense	0.7506	likely pathogenic · top 6% in AGT
REVEL	0.883	moderately pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 7,679 bp · p 0.88 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P382A vs ClinVar P373A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000847% European (non-Finnish) · 10/1,180,042 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.00062% 10/1,614,094 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.Pro373Ala
Coding: c.1117C>G
MANE Select: NM_001384479
Type: single nucleotide variant
Location: chr1:230704318 (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 373: 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 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
AGT p.Arg165Gln Uncertain significance ★★ same condition
AGT p.Arg366Leu 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-pro373ala (accessed [today's date]).

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