Is AGBL5 p.Arg487Gln (c.1460G>A) pathogenic?

AGBL5 p.Arg487Gln (c.1460G>A) is classified Uncertain significance in AGBL5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-05-07). AlphaMissense: ambiguous (0.358); Rare (popmax 0.102%, eas); Associated with Inborn genetic diseases.

What condition is associated with AGBL5 p.Arg487Gln (c.1460G>A)?

AGBL5 p.Arg487Gln (c.1460G>A) is associated with Inborn genetic diseases, inherited retinal dystrophy (ClinVar).

How common is AGBL5 p.Arg487Gln (c.1460G>A) in the general population?

AGBL5 p.Arg487Gln (c.1460G>A) is rare (popmax 0.102%, eas) (gnomAD).

What do computational predictors say about AGBL5 p.Arg487Gln (c.1460G>A)?

AlphaMissense predicts ambiguous (score 0.358) — an in-silico prediction, not a clinical call.

AGBL5 p.Arg487Gln

c.1460G>A · rs771255981 · VCV942623

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.358 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.102%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.358	ambiguous
REVEL	0.218	benign-leaning
SaProt	LLR -10.44	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 4,357 bp · p 1.1e-07 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.102% East Asian · 46/44,884 alleles

Filtering AF 0.0789% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0706%

Overall 0.00322% 52/1,613,776 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.102%	976
Remaining individualsnot grpmax-eligible	0.0016%	62,466
European (non-Finnish)	0.000424%	235,970

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.Arg487Gln
Coding: c.1460G>A
MANE Select: NM_021831
dbSNP: rs771255981
Type: single nucleotide variant
Location: chr2:27056717 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.36 · 10 PDB
Residue 487: 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 UniProt-annotated variant site (in rp75)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: inherited retinal dystrophy

Similar variants

AGBL5 p.Arg487Ter Pathogenic ★★ same residue
AGBL5 p.Trp592Ter Pathogenic ★★ same condition
AGBL5 p.Ala530Thr Uncertain significance ★★ ⚠ same condition
AGBL5 p.Arg111Cys Uncertain significance ★★ ⚠ same condition
AGBL5 p.Arg121His Uncertain significance ★★ ⚠ same condition
AGBL5 p.Arg147Cys Uncertain significance ★★ ⚠ same condition
AGBL5 p.Arg147Gly Uncertain significance ★★ ⚠ same condition
AGBL5 p.Arg147His 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-arg487gln (accessed [today's date]).

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