Is AGBL5 p.Pro108Arg (c.323C>G) pathogenic?

AGBL5 p.Pro108Arg (c.323C>G) is classified Likely pathogenic in AGBL5 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.9991); Very rare (popmax 0.000169%, nfe); Associated with retinitis pigmentosa 75.

What condition is associated with AGBL5 p.Pro108Arg (c.323C>G)?

AGBL5 p.Pro108Arg (c.323C>G) is associated with retinitis pigmentosa 75 (ClinVar).

How common is AGBL5 p.Pro108Arg (c.323C>G) in the general population?

AGBL5 p.Pro108Arg (c.323C>G) is very rare (popmax 0.000169%, nfe) (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.Pro108Arg (c.323C>G)?

AlphaMissense predicts likely pathogenic (score 0.9991) — an in-silico prediction, not a clinical call.

AGBL5 p.Pro108Arg

c.323C>G · rs1271339736 · VCV1184585

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9991 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa 75

Computational evidence

Protein change
AlphaMissense	0.9991	likely pathogenic ✓ concordant with ClinVar · top 1% in AGBL5
REVEL	0.706	pathogenic-leaning
SaProt	LLR -14.97	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 4,357 bp · p 1.1e-07 · regional, not allelic
Overall
CADD	29.3	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 0.000169% European (non-Finnish) · 2/1,180,038 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,814 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.Pro108Arg
Coding: c.323C>G
MANE Select: NM_021831
dbSNP: rs1271339736
Type: single nucleotide variant
Location: chr2:27053509 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.36 · 10 PDB
Residue 108: 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; also found in a patient with a usher-like phenotype encompassing rp and hearing loss)

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.Arg313His Uncertain significance ★★ ⚠ same condition
AGBL5 p.Gln868Lys Uncertain significance ★★ ⚠ same condition
AGBL5 p.Arg792Gln Benign/Likely benign ★★ 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.Gly105fs 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-pro108arg (accessed [today's date]).

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