Is ABTB3 p.Pro92Arg (c.275C>G) pathogenic?

ABTB3 p.Pro92Arg (c.275C>G) is classified Uncertain significance in ABTB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-22). AlphaMissense: ambiguous (0.5188); Very rare (popmax 0.00454%, eas).

How common is ABTB3 p.Pro92Arg (c.275C>G) in the general population?

ABTB3 p.Pro92Arg (c.275C>G) is very rare (popmax 0.00454%, eas) (gnomAD).

What do computational predictors say about ABTB3 p.Pro92Arg (c.275C>G)?

AlphaMissense predicts ambiguous (score 0.5188) — an in-silico prediction, not a clinical call.

ABTB3 p.Pro92Arg

c.275C>G · rs773601656 · VCV3133177

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5188 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00454%, eas)

Computational evidence

Protein change
AlphaMissense	0.5188	ambiguous
REVEL	0.441	indeterminate
SaProt	LLR -5.36	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 291 kb · p 0.39 · regional, not allelic
Overall
CADD	28.0	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 0.00454% East Asian · 2/44,048 alleles

Filtering AF 0.000753% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000282%

Overall 0.000253% 4/1,581,972 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00454%	22,024
South Asian	0.00113%	88,500
European (non-Finnish)	8.55e-05%	1,169,782

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.Pro92Arg
Coding: c.275C>G
MANE Select: NM_001018072
dbSNP: rs773601656
Type: single nucleotide variant
Location: chr12:107319215 (GRCh38)
Structure: AlphaFold pLDDT 73.18

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

Similar variants

ABTB3 p.Pro92Leu 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-pro92arg (accessed [today's date]).

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