Is AGTR1 p.Phe248fs (c.742_743del) pathogenic?

AGTR1 p.Phe248fs (c.742743del) is classified Uncertain significance in AGTR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-02). Very rare (popmax 0.005%, amr).

How common is AGTR1 p.Phe248fs (c.742_743del) in the general population?

AGTR1 p.Phe248fs (c.742_743del) is very rare (popmax 0.005%, amr) (gnomAD).

AGTR1 p.Phe248fs

c.742_743del · rs752692489 · VCV3361382

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 0.82, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,000 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000205% 3/1,460,900 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: AGTR1
Protein: p.Phe248fs
Coding: c.742_743del
MANE Select: NM_000685
dbSNP: rs752692489
Type: Deletion
Location: chr3:148741775 (GRCh38)
Gene constraint: LOEUF 1.113 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.55 · 14 PDB
Residue 248: a disulfide bond; an α-helix

Full AGTR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGTR1 p.Leu78fs Pathogenic/Likely pathogenic ★★ same type
AGTR1 p.Pro233fs Likely pathogenic ★★ same type
AGTR1 p.Ala114fs Likely pathogenic ★ same type
AGTR1 p.Phe293fs Likely pathogenic ★ same type
AGTR1 p.Tyr56fs Likely pathogenic ★ same type
AGTR1 p.Arg13fs Uncertain significance ★ same type
AGTR1 p.Cys355fs Uncertain significance ★ same type
AGTR1 p.Pro95fs 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/agtr1-p-phe248fs (accessed [today's date]).

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