Is AGTPBP1 p.Phe394fs (c.1182del) pathogenic?

AGTPBP1 p.Phe394fs (c.1182del) is classified Pathogenic in AGTPBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-21). Very rare (popmax 0.000849%, nfe).

How common is AGTPBP1 p.Phe394fs (c.1182del) in the general population?

AGTPBP1 p.Phe394fs (c.1182del) is very rare (popmax 0.000849%, nfe) (gnomAD).

AGTPBP1 p.Phe394fs

c.1182del · rs1331302673 · VCV2506865

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000849%, 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	predicted	premature termination codon in exon 12 of 26
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000849% European (non-Finnish) · 10/1,177,898 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000686% 10/1,458,034 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: AGTPBP1
Protein: p.Phe394fs
Coding: c.1182del
MANE Select: NM_001330701
dbSNP: rs1331302673
Type: Deletion
Location: chr9:85646324 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.95
Residue 394: a UniProt-annotated variant site (in condca)

Full AGTPBP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGTPBP1 p.Gln274fs Pathogenic ★ same type
AGTPBP1 p.Tyr964Terfs Pathogenic ★ same type
AGTPBP1 c.-66del Conflicting classifications of pathogenicity ★ same type
AGTPBP1 p.Thr226del 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/agtpbp1-p-phe394fs (accessed [today's date]).

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