Is AGBL5 p.Ala428fs (c.1281dup) pathogenic?

AGBL5 p.Ala428fs (c.1281dup) is classified Pathogenic in AGBL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-15). Absent from gnomAD.

How common is AGBL5 p.Ala428fs (c.1281dup) in the general population?

AGBL5 p.Ala428fs (c.1281dup) is absent from gnomAD (gnomAD).

AGBL5 p.Ala428fs

c.1281dup · rs2465465952 · VCV2007082

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 7 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AGBL5
Protein: p.Ala428fs
Coding: c.1281dup
MANE Select: NM_021831
dbSNP: rs2465465952
Type: Duplication
Location: chr2:27056052 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.36 · 10 PDB
Residue 428: 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 β-strand

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

Similar variants

AGBL5 p.Ala428Thr Uncertain significance ★ ⚠ same residue
AGBL5 c.2090-2dup Uncertain significance ★★ same type
AGBL5 c.216-14dup Likely benign ★★ same type
AGBL5 c.552-9dup Benign/Likely benign ★★ same type
AGBL5 p.Arg549fs Pathogenic ★ same type
AGBL5 p.Asn625fs Pathogenic ★ same type
AGBL5 p.His141fs Pathogenic ★ same type
AGBL5 p.Leu247fs 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/agbl5-p-ala428fs (accessed [today's date]).

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