Is ABTB3 p.Pro43Arg (c.128C>G) pathogenic?

ABTB3 p.Pro43Arg (c.128C>G) is classified Uncertain significance in ABTB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely benign (0.1214); Absent from gnomAD v4.1.

How common is ABTB3 p.Pro43Arg (c.128C>G) in the general population?

ABTB3 p.Pro43Arg (c.128C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABTB3 p.Pro43Arg (c.128C>G)?

AlphaMissense predicts likely benign (score 0.1214) — an in-silico prediction, not a clinical call.

ABTB3 p.Pro43Arg

c.128C>G · rs2499836450 · VCV2490649

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1214 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1214	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -7.02	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 7.5	GERP 1.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 291 kb · p 0.39 · regional, not allelic
Overall
CADD	26.6	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: ABTB3
Protein: p.Pro43Arg
Coding: c.128C>G
MANE Select: NM_001018072
dbSNP: rs2499836450
Type: single nucleotide variant
Location: chr12:107319068 (GRCh38)
Structure: AlphaFold pLDDT 73.18

Full ABTB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABTB3 p.Pro43Ala Uncertain significance ★ ⚠ same residue
ABTB3 c.1135+525T>A Uncertain significance ★ same type
ABTB3 p.Ala1019Val Uncertain significance ★ same type
ABTB3 p.Ala119Glu Uncertain significance ★ ⚠ same type
ABTB3 p.Ala130Thr Uncertain significance ★ ⚠ same type
ABTB3 p.Ala147Ser Uncertain significance ★ ⚠ same type
ABTB3 p.Ala147Val Uncertain significance ★ ⚠ same type
ABTB3 p.Ala176Glu 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/abtb3-p-pro43arg (accessed [today's date]).

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