Is AEBP2 p.Asp459Asn (c.1375G>A) pathogenic?

AEBP2 p.Asp459Asn (c.1375G>A) is classified Uncertain significance in AEBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely pathogenic (0.9836); Absent from gnomAD v4.1.

How common is AEBP2 p.Asp459Asn (c.1375G>A) in the general population?

AEBP2 p.Asp459Asn (c.1375G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AEBP2 p.Asp459Asn (c.1375G>A)?

AlphaMissense predicts likely pathogenic (score 0.9836) — an in-silico prediction, not a clinical call.

AEBP2 p.Asp459Asn

c.1375G>A · VCV4020763

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9836 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9836	likely pathogenic
REVEL	0.588	indeterminate
SaProt	LLR -7.87	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 78 kb · p 4.6e-19 · regional, not allelic
Overall
CADD	32.0	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: AEBP2
Protein: p.Asp459Asn
Coding: c.1375G>A
MANE Select: NM_153207
Type: single nucleotide variant
Location: chr12:19514678 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 63.62 · 21 PDB
Residue 459: an α-helix; the 'interaction with suz12' region

Full AEBP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AEBP2 p.Ala198Pro Uncertain significance ★ ⚠ same type
AEBP2 p.Ala33Pro Uncertain significance ★ ⚠ same type
AEBP2 p.Ala4Ser Uncertain significance ★ ⚠ same type
AEBP2 p.Arg138Ser Uncertain significance ★ ⚠ same type
AEBP2 p.Arg16Pro Uncertain significance ★ ⚠ same type
AEBP2 p.Asn273Thr Uncertain significance ★ ⚠ same type
AEBP2 p.Asn336Asp Uncertain significance ★ ⚠ same type
AEBP2 p.Asn336Ser 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/aebp2-p-asp459asn (accessed [today's date]).

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