Is AGXT p.Val266fs (c.795del) pathogenic?

AGXT p.Val266fs (c.795del) is classified Pathogenic in AGXT (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-06). Very rare (popmax 0.000593%, nfe).

How common is AGXT p.Val266fs (c.795del) in the general population?

AGXT p.Val266fs (c.795del) is very rare (popmax 0.000593%, nfe) (gnomAD).

AGXT p.Val266fs

c.795del · rs2106430885 · VCV1069766

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000593%, 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 8 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.7	GERP -2.6

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,179,962 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000479% 7/1,461,866 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: AGXT
Protein: p.Val266fs
Coding: c.795del
MANE Select: NM_000030
dbSNP: rs2106430885
Type: Deletion
Location: chr2:240875950 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 98.30 · 17 PDB
Residue 266: an α-helix

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

Similar variants

AGXT p.Val266Ile Uncertain significance ★★ ⚠ same residue
AGXT c.359-1_382del Pathogenic ★★ same type
AGXT c.424-66_425del Likely pathogenic ★★ same type
AGXT c.679_680+2del Pathogenic ★★ same type
AGXT p.Ala325fs Pathogenic/Likely pathogenic ★★ same type
AGXT p.Gln110fs Pathogenic ★★ same type
AGXT p.Gln145fs Pathogenic/Likely pathogenic ★★ same type
AGXT p.Leu151fs Pathogenic ★★ 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/agxt-p-val266fs (accessed [today's date]).

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