Is AGT p.Ser7Arg (c.21C>A) pathogenic?

AGT p.Ser7Arg (c.21C>A) is classified Uncertain significance in AGT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-02). AlphaMissense: ambiguous (0.3565); Very rare (popmax 0.000169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AGT p.Ser7Arg (c.21C>A)?

AGT p.Ser7Arg (c.21C>A) is associated with Inborn genetic diseases, renal tubular dysgenesis of genetic origin (ClinVar).

How common is AGT p.Ser7Arg (c.21C>A) in the general population?

AGT p.Ser7Arg (c.21C>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about AGT p.Ser7Arg (c.21C>A)?

AlphaMissense predicts ambiguous (score 0.3565) — an in-silico prediction, not a clinical call.

AGT p.Ser7Arg

c.21C>A · VCV3276609

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3565 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3565	ambiguous
REVEL	0.155	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -2, phastCons 0.008
Regional constraint	o/e 1.01	unconstrained · MANE · 7,679 bp · p 0.88 · regional, not allelic
Overall
CADD	14.2	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 S16R vs ClinVar S7R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,030 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,900 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.Ser7Arg
Coding: c.21C>A
MANE Select: NM_001384479
Type: single nucleotide variant
Location: chr1:230710803 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: renal tubular dysgenesis of genetic origin

Similar variants

AGT p.Ser7= Conflicting classifications of pathogenicity ★ 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
AGT p.Arg165Gln 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-ser7arg (accessed [today's date]).

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