Is ABTB2 p.Arg708Trp (c.2122C>T) pathogenic?

ABTB2 p.Arg708Trp (c.2122C>T) is classified Uncertain significance in ABTB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-27). AlphaMissense: likely benign (0.1205); Very rare (popmax 0.0022%, sas).

How common is ABTB2 p.Arg708Trp (c.2122C>T) in the general population?

ABTB2 p.Arg708Trp (c.2122C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about ABTB2 p.Arg708Trp (c.2122C>T)?

AlphaMissense predicts likely benign (score 0.1205) — an in-silico prediction, not a clinical call.

ABTB2 p.Arg708Trp

c.2122C>T · VCV3451898

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1205 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1205	likely benign
REVEL	0.243	benign-leaning
SaProt	LLR -10.13	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -3.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 205 kb · p 0.0006 · regional, not allelic
Overall
CADD	24.8	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 0.0022% South Asian · 2/91,080 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000992% 16/1,613,144 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,540
Admixed American	0.00167%	60,022
Remaining individualsnot grpmax-eligible	0.0016%	62,496
African / African-American	0.00133%	75,052
European (non-Finnish)	0.000932%	107,274

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.Arg708Trp
Coding: c.2122C>T
MANE Select: NM_145804
Type: single nucleotide variant
Location: chr11:34162672 (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.Arg708Gly 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
ABTB2 p.Ala301Pro 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-arg708trp (accessed [today's date]).

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