Is AGBL5 p.Ala486Val (c.1457C>T) pathogenic?

AGBL5 p.Ala486Val (c.1457C>T) is classified Uncertain significance in AGBL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-15). AlphaMissense: ambiguous (0.4742); Absent from gnomAD v4.1.

How common is AGBL5 p.Ala486Val (c.1457C>T) in the general population?

AGBL5 p.Ala486Val (c.1457C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGBL5 p.Ala486Val (c.1457C>T)?

AlphaMissense predicts ambiguous (score 0.4742) — an in-silico prediction, not a clinical call.

AGBL5 p.Ala486Val

c.1457C>T · rs1668448156 · VCV1909123

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4742 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4742	ambiguous
REVEL	0.336	indeterminate
SaProt	LLR -7.18	tolerated
Splicing
SpliceAI	Δ0.44	donor gain · deltas
Pangolin	Δ0.20	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 4,357 bp · p 1.1e-07 · regional, not allelic
Overall
CADD	34.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AGBL5
Protein: p.Ala486Val
Coding: c.1457C>T
MANE Select: NM_021831
dbSNP: rs1668448156
Type: single nucleotide variant
Location: chr2:27056714 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.36 · 10 PDB
Residue 486: the peptidase m14 domain; a UniProt-annotated variant site (found in patients with a usher-like phenotype encompassing rp and hearing loss; likely pathogenic)

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

Similar variants

AGBL5 p.Ala486= Likely benign ★★ same residue
AGBL5 p.Ala486Gly Uncertain significance ★ ⚠ same residue
AGBL5 p.Arg220Ter Pathogenic ★★ same type
AGBL5 p.Arg487Ter Pathogenic ★★ same type
AGBL5 p.Trp592Ter Pathogenic ★★ same type
AGBL5 p.Tyr485Ter Pathogenic/Likely pathogenic ★★ same type
AGBL5 c.2355+4A>G Uncertain significance ★★ same type
AGBL5 c.551+5C>A Uncertain significance ★★ same type

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-ala486val (accessed [today's date]).

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