Is AGBL5 p.Arg673Pro (c.2018G>C) pathogenic?

AGBL5 p.Arg673Pro (c.2018G>C) is classified Uncertain significance in AGBL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-11). AlphaMissense: likely benign (0.1692); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AGBL5 p.Arg673Pro (c.2018G>C)?

AGBL5 p.Arg673Pro (c.2018G>C) is associated with Inborn genetic diseases (ClinVar).

How common is AGBL5 p.Arg673Pro (c.2018G>C) in the general population?

AGBL5 p.Arg673Pro (c.2018G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGBL5 p.Arg673Pro (c.2018G>C)?

AlphaMissense predicts likely benign (score 0.1692) — an in-silico prediction, not a clinical call.

AGBL5 p.Arg673Pro

c.2018G>C · VCV3506436

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1692 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1692	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -6.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 2.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 13 kb · p 0.75 · regional, not allelic
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AGBL5
Protein: p.Arg673Pro
Coding: c.2018G>C
MANE Select: NM_021831
Type: single nucleotide variant
Location: chr2:27059333 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.36 · 10 PDB
Residue 673: 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

Disease context

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

Similar variants

AGBL5 p.Arg673Trp Uncertain significance ★★ ⚠ same residue
AGBL5 p.Arg673= Likely benign ★★ same residue
AGBL5 p.Arg673Gln Uncertain significance ★ ⚠ same residue
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

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-arg673pro (accessed [today's date]).

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