Is AGBL5 p.Ser682= (c.2046T>A) pathogenic?

AGBL5 p.Ser682= (c.2046T>A) is classified Benign in AGBL5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). Low-frequency (popmax 3.98%, afr); Associated with retinitis pigmentosa 75.

What condition is associated with AGBL5 p.Ser682= (c.2046T>A)?

AGBL5 p.Ser682= (c.2046T>A) is associated with retinitis pigmentosa 75 (ClinVar).

How common is AGBL5 p.Ser682= (c.2046T>A) in the general population?

AGBL5 p.Ser682= (c.2046T>A) is low-frequency (popmax 3.98%, afr) (gnomAD).

How is Retinitis pigmentosa inherited?

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

AGBL5 p.Ser682=

c.2046T>A · rs34931609 · VCV771695

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.98%, afr)

Conditions

retinitis pigmentosa 75

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 -1.6	GERP -1.8
Overall
CADD	3.296	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.98% African / African-American · 2,988/75,066 alleles

Filtering AF 3.86% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.81%

Overall 0.956% 15,437/1,614,222 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.98%	25
Ashkenazi Jewishnot grpmax-eligible	1.33%	75
Middle Eastern	1.09%	92
Remaining individualsnot grpmax-eligible	0.904%	111
European (non-Finnish)	0.876%	114
Admixed American	0.811%	123
Amishnot grpmax-eligible	0.768%	130
Finnishnot grpmax-eligible	0.464%	216
South Asian	0.33%	303
East Asian	0.00223%	44,880

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.Ser682=
Coding: c.2046T>A
MANE Select: NM_021831
dbSNP: rs34931609
Type: single nucleotide variant
Location: chr2:27059361 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.36 · 10 PDB
Residue 682: 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.Arg313His Uncertain significance ★★ ⚠ same condition
AGBL5 p.Gln868Lys Uncertain significance ★★ ⚠ same condition
AGBL5 p.Arg792Gln Benign/Likely 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
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-ser682 (accessed [today's date]).

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