Is AEBP1 p.Pro289Arg (c.866C>G) pathogenic?

AEBP1 p.Pro289Arg (c.866C>G) is classified Uncertain significance in AEBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-18). AlphaMissense: likely benign (0.0819); Absent from gnomAD v4.1.

How common is AEBP1 p.Pro289Arg (c.866C>G) in the general population?

AEBP1 p.Pro289Arg (c.866C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AEBP1 p.Pro289Arg (c.866C>G)?

AlphaMissense predicts likely benign (score 0.0819) — an in-silico prediction, not a clinical call.

AEBP1 p.Pro289Arg

c.866C>G · VCV4733449

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0819 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0819	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -7.01	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 0.09	GERP -0.96
Regional constraint	o/e 0.93	unconstrained · MANE · 9,592 bp · p 0.004 · regional, not allelic
Overall
CADD	15.93	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: AEBP1
Protein: p.Pro289Arg
Coding: c.866C>G
MANE Select: NM_001129
Type: single nucleotide variant
Location: chr7:44108010 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.99
Residue 289: the 'disordered' region

Full AEBP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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AEBP1 p.Arg595Ter Pathogenic ★★ same type
AEBP1 p.Cys581Ter Pathogenic/Likely pathogenic ★★ same type
AEBP1 p.Cys868Ter Likely pathogenic ★★ same type
AEBP1 p.Gln781Ter Pathogenic/Likely pathogenic ★★ same type
AEBP1 p.Tyr428Ter Pathogenic/Likely pathogenic ★★ 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/aebp1-p-pro289arg (accessed [today's date]).

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