Is AGBL5 p.Arg792Gln (c.2375G>A) pathogenic?

AGBL5 p.Arg792Gln (c.2375G>A) is classified Benign/Likely benign in AGBL5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0877); Low-frequency (popmax 3.99%, afr); Associated with retinitis pigmentosa 75.

What condition is associated with AGBL5 p.Arg792Gln (c.2375G>A)?

AGBL5 p.Arg792Gln (c.2375G>A) is associated with retinitis pigmentosa 75 (ClinVar).

How common is AGBL5 p.Arg792Gln (c.2375G>A) in the general population?

AGBL5 p.Arg792Gln (c.2375G>A) is low-frequency (popmax 3.99%, afr) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about AGBL5 p.Arg792Gln (c.2375G>A)?

AlphaMissense predicts likely benign (score 0.0877) — an in-silico prediction, not a clinical call.

AGBL5 p.Arg792Gln

c.2375G>A · rs61354909 · VCV789558

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0877 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.99%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa 75

Computational evidence

Protein change
AlphaMissense	0.0877	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -6.64	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 0.48	GERP -2.4, phastCons 0.99
Regional constraint	o/e 1.01	unconstrained · MANE · 13 kb · p 0.75 · regional, not allelic
Overall
CADD	16.85	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 3.99% African / African-American · 2,991/75,042 alleles

Filtering AF 3.87% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.82%

Overall 0.212% 3,418/1,614,080 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.99%	25
Admixed American	0.295%	339
Remaining individualsnot grpmax-eligible	0.291%	343
Middle Eastern	0.116%	866
South Asian	0.0154%	6,506
East Asian	0.0111%	8,976
European (non-Finnish)	0.00347%	28,779
Finnishnot grpmax-eligible	0.00156%	64,036

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.Arg792Gln
Coding: c.2375G>A
MANE Select: NM_021831
dbSNP: rs61354909
Type: single nucleotide variant
Location: chr2:27069592 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.36 · 10 PDB
Residue 792: 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

retinitis pigmentosa 75 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

AGBL5 p.Arg792Trp Uncertain significance ★★ ⚠ same residue
AGBL5 p.Arg313His Uncertain significance ★★ ⚠ same condition
AGBL5 p.Gln868Lys Uncertain significance ★★ ⚠ same condition
AGBL5 p.Ser682= Benign ★★ same condition
AGBL5 c.2242+1G>A Likely pathogenic ★ same condition
AGBL5 p.Asp295Asn Pathogenic ★ same condition
AGBL5 p.Arg276Trp Conflicting classifications of pathogenicity ★ ⚠ same condition
AGBL5 p.Pro108Arg Likely pathogenic 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-arg792gln (accessed [today's date]).

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