Is AEBP1 p.Lys89Asn (c.267G>C) pathogenic?

AEBP1 p.Lys89Asn (c.267G>C) is classified Uncertain significance in AEBP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-24). AlphaMissense: likely benign (0.2869); Ultra-rare (popmax 0.0582%, nfe).

How common is AEBP1 p.Lys89Asn (c.267G>C) in the general population?

AEBP1 p.Lys89Asn (c.267G>C) is ultra-rare (popmax 0.0582%, nfe) (gnomAD).

What do computational predictors say about AEBP1 p.Lys89Asn (c.267G>C)?

AlphaMissense predicts likely benign (score 0.2869) — an in-silico prediction, not a clinical call.

AEBP1 p.Lys89Asn

c.267G>C · rs139078339 · VCV1490068

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2869 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0582%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2869	likely benign
REVEL	0.354	indeterminate
SaProt	LLR -8.94	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.23, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 9,592 bp · p 0.004 · regional, not allelic
Overall
CADD	20.2	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

Grpmax group 0.0582% European (non-Finnish) · 684/1,175,618 alleles

Filtering AF 0.0545% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0531%

Overall 0.0463% 741/1,600,674 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0582%	1,719
Remaining individualsnot grpmax-eligible	0.0484%	2,065
Finnishnot grpmax-eligible	0.0223%	4,489
Admixed American	0.0107%	9,383
African / African-American	0.00942%	10,618

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: AEBP1
Protein: p.Lys89Asn
Coding: c.267G>C
MANE Select: NM_001129
dbSNP: rs139078339
Type: single nucleotide variant
Location: chr7:44106559 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.99
Residue 89: the 'disordered' region

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

Similar variants

AEBP1 p.Lys89= Likely benign ★★ same residue
AEBP1 c.1018+1G>A Likely pathogenic ★★ same type
AEBP1 c.1630+1G>A Pathogenic ★★ same type
AEBP1 c.1630+2T>A Pathogenic ★★ same type
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

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-lys89asn (accessed [today's date]).

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