Is AGBL5 p.Arg147Cys (c.439C>T) pathogenic?

AGBL5 p.Arg147Cys (c.439C>T) is classified Uncertain significance in AGBL5 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-08-26). AlphaMissense: ambiguous (0.3676); Rare (popmax 0.12%, sas); Associated with Inborn genetic diseases.

What condition is associated with AGBL5 p.Arg147Cys (c.439C>T)?

AGBL5 p.Arg147Cys (c.439C>T) is associated with Inborn genetic diseases, inherited retinal dystrophy (ClinVar).

How common is AGBL5 p.Arg147Cys (c.439C>T) in the general population?

AGBL5 p.Arg147Cys (c.439C>T) is rare (popmax 0.12%, sas) (gnomAD).

What do computational predictors say about AGBL5 p.Arg147Cys (c.439C>T)?

AlphaMissense predicts ambiguous (score 0.3676) — an in-silico prediction, not a clinical call.

AGBL5 p.Arg147Cys

c.439C>T · rs144135243 · VCV837462

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.3676 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.12%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3676	ambiguous
REVEL	0.262	benign-leaning
SaProt	LLR -7.74	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 4,357 bp · p 1.1e-07 · regional, not allelic
Overall
CADD	33.0	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 0.12% South Asian · 109/91,076 alleles

Filtering AF 0.101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0946%

Overall 0.0196% 317/1,614,090 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.12%	836
East Asian	0.0847%	1,181
European (non-Finnish)	0.0134%	7,468
Remaining individualsnot grpmax-eligible	0.0128%	7,814
African / African-American	0.004%	25,001
Finnishnot grpmax-eligible	0.00156%	64,028

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.Arg147Cys
Coding: c.439C>T
MANE Select: NM_021831
dbSNP: rs144135243
Type: single nucleotide variant
Location: chr2:27053947 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.36 · 10 PDB
Residue 147: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: inherited retinal dystrophy

Similar variants

AGBL5 p.Arg147Gly Uncertain significance ★★ ⚠ same residue
AGBL5 p.Arg147His Uncertain significance ★★ ⚠ same residue
AGBL5 p.Trp592Ter Pathogenic ★★ same condition
AGBL5 p.Ala530Thr Uncertain significance ★★ ⚠ same condition
AGBL5 p.Arg111Cys Uncertain significance ★★ ⚠ same condition
AGBL5 p.Arg121His Uncertain significance ★★ ⚠ same condition
AGBL5 p.Arg174His Uncertain significance ★★ ⚠ same condition
AGBL5 p.Arg204His 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-arg147cys (accessed [today's date]).

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