Is ABTB3 p.Pro820Arg (c.2459C>G) pathogenic?

ABTB3 p.Pro820Arg (c.2459C>G) is classified Uncertain significance in ABTB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-13). AlphaMissense: likely pathogenic (0.7038); Ultra-rare (popmax 0.0245%, eas).

How common is ABTB3 p.Pro820Arg (c.2459C>G) in the general population?

ABTB3 p.Pro820Arg (c.2459C>G) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

What do computational predictors say about ABTB3 p.Pro820Arg (c.2459C>G)?

AlphaMissense predicts likely pathogenic (score 0.7038) — an in-silico prediction, not a clinical call.

ABTB3 p.Pro820Arg

c.2459C>G · rs767141861 · VCV2598778

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7038 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7038	likely pathogenic
REVEL	0.501	indeterminate
SaProt	LLR -7.38	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 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 48 kb · p 1.1e-08 · regional, not allelic
Overall
CADD	26.4	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 0.0245% East Asian · 11/44,844 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.000807% 13/1,611,672 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,077
African / African-American	0.00134%	74,890
European (non-Finnish)	8.48e-05%	1,179,133

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.Pro820Arg
Coding: c.2459C>G
MANE Select: NM_001018072
dbSNP: rs767141861
Type: single nucleotide variant
Location: chr12:107619992 (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-pro820arg (accessed [today's date]).

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