Is AGBL5 p.Glu424= (c.1272G>A) pathogenic?

AGBL5 p.Glu424= (c.1272G>A) is classified Uncertain significance in AGBL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). Very rare (popmax 8.47e-05%, nfe); Associated with inherited retinal dystrophy.

What condition is associated with AGBL5 p.Glu424= (c.1272G>A)?

AGBL5 p.Glu424= (c.1272G>A) is associated with inherited retinal dystrophy (ClinVar).

How common is AGBL5 p.Glu424= (c.1272G>A) in the general population?

AGBL5 p.Glu424= (c.1272G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

AGBL5 p.Glu424=

c.1272G>A · rs2148277038 · VCV3028766

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 0.33, phastCons 1
Overall
CADD	9.113	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,044 alleles

Overall 6.84e-05% 1/1,461,890 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: AGBL5
Protein: p.Glu424=
Coding: c.1272G>A
MANE Select: NM_021831
dbSNP: rs2148277038
Type: single nucleotide variant
Location: chr2:27056045 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.36 · 10 PDB
Residue 424: the peptidase m14 domain; a UniProt-annotated variant site (found in patients with a usher-like phenotype encompassing rp and hearing loss; likely pathogenic); a turn

Full AGBL5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AGBL5 p.Trp592Ter Pathogenic ★★ same condition
AGBL5 p.Arg147Cys Uncertain significance ★★ ⚠ same condition
AGBL5 p.Arg341His Uncertain significance ★★ ⚠ same condition
AGBL5 p.Arg487Gln Uncertain significance ★★ ⚠ same condition
AGBL5 p.Arg489His Uncertain significance ★★ ⚠ same condition
AGBL5 p.Arg537His Uncertain significance ★★ ⚠ same condition
AGBL5 p.Arg598His Uncertain significance ★★ ⚠ same condition
AGBL5 p.Arg673Trp Uncertain significance ★★ ⚠ same condition

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/agbl5-p-glu424 (accessed [today's date]).

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