Is ABTB2 p.Arg28Pro (c.83G>C) pathogenic?

ABTB2 p.Arg28Pro (c.83G>C) is classified Uncertain significance in ABTB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: ambiguous (0.3436); Very rare (popmax 0.00137%, afr).

How common is ABTB2 p.Arg28Pro (c.83G>C) in the general population?

ABTB2 p.Arg28Pro (c.83G>C) is very rare (popmax 0.00137%, afr) (gnomAD).

What do computational predictors say about ABTB2 p.Arg28Pro (c.83G>C)?

AlphaMissense predicts ambiguous (score 0.3436) — an in-silico prediction, not a clinical call.

ABTB2 p.Arg28Pro

c.83G>C · rs555345847 · VCV3133112

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3436 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00137%, afr)

Computational evidence

Protein change
AlphaMissense	0.3436	ambiguous
REVEL	0.619	indeterminate
SaProt	LLR -5.93	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 205 kb · p 0.0006 · regional, not allelic
Overall
CADD	24.4	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 0.00137% African / African-American · 1/73,136 alleles

Overall 7.2e-05% 1/1,389,760 alleles · very rare

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.Arg28Pro
Coding: c.83G>C
MANE Select: NM_145804
dbSNP: rs555345847
Type: single nucleotide variant
Location: chr11:34357501 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.05

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

Similar variants

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
ABTB2 p.Ala301Thr 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-arg28pro (accessed [today's date]).

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