Is AGBL5 p.Arg813fs (c.2437dup) pathogenic?

AGBL5 p.Arg813fs (c.2437dup) is classified Uncertain significance in AGBL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-24). Very rare (popmax 0.000508%, nfe).

How common is AGBL5 p.Arg813fs (c.2437dup) in the general population?

AGBL5 p.Arg813fs (c.2437dup) is very rare (popmax 0.000508%, nfe) (gnomAD).

AGBL5 p.Arg813fs

c.2437dup · rs759542168 · VCV1060377

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000508%, 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 14 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.057	GERP -4.2

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000508% European (non-Finnish) · 6/1,179,970 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.00041% 6/1,461,836 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.Arg813fs
Coding: c.2437dup
MANE Select: NM_021831
dbSNP: rs759542168
Type: Duplication
Location: chr2:27069648 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.36 · 10 PDB
Residue 813: a UniProt-annotated variant site (found in patients with a usher-like phenotype encompassing rp and hearing loss; likely pathogenic); a UniProt-annotated variant site (in rp75); the 'disordered' region

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

Similar variants

AGBL5 p.Arg813Gly Uncertain significance ★★ ⚠ same residue
AGBL5 p.Arg813Gln Benign/Likely benign ★★ same residue
AGBL5 p.Arg813Pro Uncertain significance ★ same residue
AGBL5 p.Arg813Trp 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.Ala428fs 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-arg813fs (accessed [today's date]).

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