Is AGXT p.Ser275fs (c.823_824del) pathogenic?

AGXT p.Ser275fs (c.823824del) is classified Pathogenic in AGXT (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-04). Very rare (popmax 0.0011%, sas).

How common is AGXT p.Ser275fs (c.823_824del) in the general population?

AGXT p.Ser275fs (c.823_824del) is very rare (popmax 0.0011%, sas) (gnomAD).

AGXT p.Ser275fs

c.823_824del · rs180177273 · VCV1074073

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 7.6	GERP 1.3, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,076 alleles

Overall 6.84e-05% 1/1,461,868 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.Ser275fs
Coding: c.823_824del
MANE Select: NM_000030
dbSNP: rs180177273
Type: Microsatellite
Location: chr2:240875974 (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 275: an α-helix

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

Similar variants

AGXT p.Ser275Arg Likely pathogenic ★ same residue
AGXT p.Ser275Asn Likely pathogenic ★ same residue
AGXT p.Ser275Ile Likely pathogenic ★ same residue
AGXT p.Ala85fs Pathogenic/Likely pathogenic ★★ same type
AGXT p.Val324fs Pathogenic ★★ same type
AGXT c.165+58_165+59insACGGAAGAGGGGAGGGGTCACTGCTTCCTCACTCGGGGGGCCTGGGTCTCACCCCTGTACCCACCCACAGATC Benign ★★ same type
AGXT c.166-57_166-56insTTCCTCACTCGGGGGGCCTGGGTCTCACCCCTGTACCCACCCACAGATCGTGGACGAGGGAAGGGGGTCACTGC Benign ★★ same type
AGXT c.358+56_358+64del Benign ★★ 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-ser275fs (accessed [today's date]).

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