Is AGBL5 p.Arg80Trp (c.238C>T) pathogenic?

AGBL5 p.Arg80Trp (c.238C>T) is classified Uncertain significance in AGBL5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-26). AlphaMissense: likely pathogenic (0.5986); Ultra-rare (popmax 0.0134%, eas); Associated with inherited retinal dystrophy.

What condition is associated with AGBL5 p.Arg80Trp (c.238C>T)?

AGBL5 p.Arg80Trp (c.238C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is AGBL5 p.Arg80Trp (c.238C>T) in the general population?

AGBL5 p.Arg80Trp (c.238C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about AGBL5 p.Arg80Trp (c.238C>T)?

AlphaMissense predicts likely pathogenic (score 0.5986) — an in-silico prediction, not a clinical call.

AGBL5 p.Arg80Trp

c.238C>T · rs762250069 · VCV3028756

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.5986 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.5986	likely pathogenic
REVEL	0.311	indeterminate
SaProt	LLR -11.91	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	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	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.0134% East Asian · 6/44,876 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00233% 34/1,461,798 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,479
European (non-Finnish)	0.00212%	47,199
Remaining individualsnot grpmax-eligible	0.0016%	62,500
African / African-American	0.00133%	74,994
South Asian	0.0011%	91,064

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.Arg80Trp
Coding: c.238C>T
MANE Select: NM_021831
dbSNP: rs762250069
Type: single nucleotide variant
Location: chr2:27053424 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.36 · 10 PDB
Residue 80: a UniProt-annotated variant site (found in patients with a usher-like phenotype encompassing rp and hearing loss; likely pathogenic); a β-strand

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AGBL5 p.Arg80Gln Uncertain significance ★★ ⚠ same residue
AGBL5 p.Arg80= Likely benign ★★ same residue
AGBL5 p.Trp592Ter Pathogenic ★★ same condition
AGBL5 p.Arg147Cys Uncertain significance ★★ ⚠ same condition
AGBL5 p.Arg341His Uncertain significance ★★ ⚠ same condition
AGBL5 p.Arg487Gln Uncertain significance ★★ ⚠ same condition
AGBL5 p.Arg489His Uncertain significance ★★ ⚠ same condition
AGBL5 p.Arg537His 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-arg80trp (accessed [today's date]).

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