Is ABTB2 p.Glu889Asp (c.2667G>T) pathogenic?

ABTB2 p.Glu889Asp (c.2667G>T) is classified Uncertain significance in ABTB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: ambiguous (0.4226); Very rare (popmax 0.00288%, nfe).

How common is ABTB2 p.Glu889Asp (c.2667G>T) in the general population?

ABTB2 p.Glu889Asp (c.2667G>T) is very rare (popmax 0.00288%, nfe) (gnomAD).

What do computational predictors say about ABTB2 p.Glu889Asp (c.2667G>T)?

AlphaMissense predicts ambiguous (score 0.4226) — an in-silico prediction, not a clinical call.

ABTB2 p.Glu889Asp

c.2667G>T · VCV3995158

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4226 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00288%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4226	ambiguous
REVEL	0.329	indeterminate
SaProt	LLR -10.16	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 205 kb · p 0.0006 · regional, not allelic
Overall
CADD	24.5	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

Grpmax group 0.00288% European (non-Finnish) · 34/1,179,962 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00229% 37/1,613,908 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00288%	34,705
South Asian	0.0022%	45,531
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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: ABTB2
Protein: p.Glu889Asp
Coding: c.2667G>T
MANE Select: NM_145804
Type: single nucleotide variant
Location: chr11:34159326 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.05
Residue 889: the btb domain

Full ABTB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABTB2 p.Glu889Lys Uncertain significance ★ ⚠ same residue
ABTB2 p.Ala122Pro Uncertain significance ★ ⚠ same type
ABTB2 p.Ala129Val Uncertain significance ★ ⚠ same type
ABTB2 p.Ala181Val Uncertain significance ★ ⚠ same type
ABTB2 p.Ala248Thr Uncertain significance ★ ⚠ same type
ABTB2 p.Ala257Thr Uncertain significance ★ ⚠ same type
ABTB2 p.Ala293Thr Uncertain significance ★ ⚠ same type
ABTB2 p.Ala301Pro 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/abtb2-p-glu889asp (accessed [today's date]).

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