Is ABTB3 p.Arg153Pro (c.458G>C) pathogenic?

ABTB3 p.Arg153Pro (c.458G>C) is classified Uncertain significance in ABTB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-10). AlphaMissense: likely pathogenic (0.6685); Very rare (popmax 0.00172%, amr).

How common is ABTB3 p.Arg153Pro (c.458G>C) in the general population?

ABTB3 p.Arg153Pro (c.458G>C) is very rare (popmax 0.00172%, amr) (gnomAD).

What do computational predictors say about ABTB3 p.Arg153Pro (c.458G>C)?

AlphaMissense predicts likely pathogenic (score 0.6685) — an in-silico prediction, not a clinical call.

ABTB3 p.Arg153Pro

c.458G>C · rs760138050 · VCV3133246

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6685 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00172%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6685	likely pathogenic
REVEL	0.626	indeterminate
SaProt	LLR -2.38	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 9.8	GERP -0.45, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 291 kb · p 0.39 · 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

Grpmax group 0.00172% Admixed American · 1/58,020 alleles

Filtering AF 0.000618% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000476%

Overall 0.000939% 15/1,596,794 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00172%	58,020
Remaining individualsnot grpmax-eligible	0.00162%	61,890
European (non-Finnish)	0.00111%	90,254

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: ABTB3
Protein: p.Arg153Pro
Coding: c.458G>C
MANE Select: NM_001018072
dbSNP: rs760138050
Type: single nucleotide variant
Location: chr12:107319398 (GRCh38)
Structure: AlphaFold pLDDT 73.18

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

Similar variants

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
ABTB3 p.Ala176Ser 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-arg153pro (accessed [today's date]).

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