Is ABTB2 p.Arg368His (c.1103G>A) pathogenic?

ABTB2 p.Arg368His (c.1103G>A) is classified Uncertain significance in ABTB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: likely benign (0.1218); Ultra-rare (popmax 0.0188%, afr).

How common is ABTB2 p.Arg368His (c.1103G>A) in the general population?

ABTB2 p.Arg368His (c.1103G>A) is ultra-rare (popmax 0.0188%, afr) (gnomAD).

What do computational predictors say about ABTB2 p.Arg368His (c.1103G>A)?

AlphaMissense predicts likely benign (score 0.1218) — an in-silico prediction, not a clinical call.

ABTB2 p.Arg368His

c.1103G>A · rs560825781 · VCV2250905

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1218 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0188%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1218	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -6.37	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 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 205 kb · p 0.0006 · regional, not allelic
Overall
CADD	26.3	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

Grpmax group 0.0188% African / African-American · 14/74,394 alleles

Filtering AF 0.0113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0091%

Overall 0.0022% 35/1,588,668 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0188%	5,314
South Asian	0.00569%	17,561
East Asian	0.00449%	22,267
Finnishnot grpmax-eligible	0.00333%	30,058
Remaining individualsnot grpmax-eligible	0.00325%	30,734
Admixed American	0.00173%	57,846
European (non-Finnish)	0.000771%	129,737

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.Arg368His
Coding: c.1103G>A
MANE Select: NM_145804
dbSNP: rs560825781
Type: single nucleotide variant
Location: chr11:34197466 (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.Arg368Cys Uncertain significance ★ ⚠ same residue
ABTB2 p.Arg368Leu Uncertain significance ★ ⚠ same residue
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

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-arg368his (accessed [today's date]).

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