Is AGBL5 p.Gln372Pro (c.1115A>C) pathogenic?

AGBL5 p.Gln372Pro (c.1115A>C) is classified Uncertain significance in AGBL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: likely benign (0.0661); Absent from gnomAD v4.1.

How common is AGBL5 p.Gln372Pro (c.1115A>C) in the general population?

AGBL5 p.Gln372Pro (c.1115A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGBL5 p.Gln372Pro (c.1115A>C)?

AlphaMissense predicts likely benign (score 0.0661) — an in-silico prediction, not a clinical call.

AGBL5 p.Gln372Pro

c.1115A>C · rs201152933 · VCV2108192

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0661 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0661	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -6.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 0.43, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 4,357 bp · p 1.1e-07 · regional, not allelic
Overall
CADD	18.51	PHRED · no single calibrated threshold — expert panels disagree

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

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.Gln372Pro
Coding: c.1115A>C
MANE Select: NM_021831
dbSNP: rs201152933
Type: single nucleotide variant
Location: chr2:27055888 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.36 · 10 PDB
Residue 372: 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.Gln372= Likely benign ★★ same residue
AGBL5 p.Gln372His Uncertain significance ★ same residue
AGBL5 p.Gln372fs Likely pathogenic ★ 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

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-gln372pro (accessed [today's date]).

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