Is AGBL5 p.Ala842= (c.2526C>T) pathogenic?

AGBL5 p.Ala842= (c.2526C>T) is classified Likely benign in AGBL5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-05). Rare (popmax 0.14%, eas); Associated with inherited retinal dystrophy.

What condition is associated with AGBL5 p.Ala842= (c.2526C>T)?

AGBL5 p.Ala842= (c.2526C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is AGBL5 p.Ala842= (c.2526C>T) in the general population?

AGBL5 p.Ala842= (c.2526C>T) is rare (popmax 0.14%, eas) (gnomAD).

AGBL5 p.Ala842=

c.2526C>T · rs529554818 · VCV1125204

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.14%, eas)

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 1.3, phastCons 1
Overall
CADD	9.692	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.14% East Asian · 63/44,896 alleles

Filtering AF 0.112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.102%

Overall 0.00427% 69/1,614,208 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.14%	713
Remaining individualsnot grpmax-eligible	0.0096%	10,418

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.Ala842=
Coding: c.2526C>T
MANE Select: NM_021831
dbSNP: rs529554818
Type: single nucleotide variant
Location: chr2:27070128 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.36 · 10 PDB
Residue 842: 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

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

Similar variants

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
AGBL5 p.Arg598His Uncertain significance ★★ ⚠ same condition
AGBL5 p.Arg673Trp 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-ala842 (accessed [today's date]).

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