Is AGTR2 p.Phe134fs (c.402del) pathogenic?

AGTR2 p.Phe134fs (c.402del) is classified Likely benign in AGTR2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2016-06-01). Ultra-rare (popmax 0.0745%, nfe).

How common is AGTR2 p.Phe134fs (c.402del) in the general population?

AGTR2 p.Phe134fs (c.402del) is ultra-rare (popmax 0.0745%, nfe) (gnomAD).

AGTR2 p.Phe134fs

c.402del · rs387906503 · VCV11717

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0745%, nfe)

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 7.6	GERP 0.27, phastCons 1
Overall
CADD	29.5	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 0.0745% European (non-Finnish) · 666/894,274 alleles

Filtering AF 0.0698% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0679%

Overall 0.0575% 695/1,208,062 alleles · ultra-rare exomes 646/1,097,460 · genomes 49/110,602 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0745%	1,343
Remaining individualsnot grpmax-eligible	0.0399%	2,505
Finnishnot grpmax-eligible	0.0108%	9,282
African / African-American	0.00881%	11,356

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: AGTR2
Protein: p.Phe134fs
Coding: c.402del
MANE Select: NM_000686
dbSNP: rs387906503
Type: Deletion
Location: chrX:116172675 (GRCh38)
Structure: AlphaFold pLDDT 82.34 · 7 PDB
Residue 134: an α-helix

Full AGTR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGTR2 p.Thr250fs 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/agtr2-p-phe134fs (accessed [today's date]).

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