Is AGT p.Trp292Ter (c.876G>A) pathogenic?

AGT p.Trp292Ter (c.876G>A) is classified Likely pathogenic in AGT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-25). Very rare (popmax 0.00134%, afr); Associated with renal tubular dysgenesis of genetic origin.

What condition is associated with AGT p.Trp292Ter (c.876G>A)?

AGT p.Trp292Ter (c.876G>A) is associated with renal tubular dysgenesis of genetic origin (ClinVar).

How common is AGT p.Trp292Ter (c.876G>A) in the general population?

AGT p.Trp292Ter (c.876G>A) is very rare (popmax 0.00134%, afr) (gnomAD).

AGT p.Trp292Ter

c.876G>A · VCV4292985

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

renal tubular dysgenesis of genetic origin

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 5
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 1.4, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,896 alleles

Overall 0.000124% 2/1,613,868 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
African / African-Americangrpmax	0.00134%	74,896

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Trp292Ter
Coding: c.876G>A
MANE Select: NM_001384479
Type: single nucleotide variant
Location: chr1:230706154 (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

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-trp292ter (accessed [today's date]).

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