Is ABTB2 p.Val741Ala (c.2222T>C) pathogenic?

ABTB2 p.Val741Ala (c.2222T>C) is classified Uncertain significance in ABTB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-08). AlphaMissense: likely pathogenic (0.8048); Very rare (popmax 0.0017%, amr).

How common is ABTB2 p.Val741Ala (c.2222T>C) in the general population?

ABTB2 p.Val741Ala (c.2222T>C) is very rare (popmax 0.0017%, amr) (gnomAD).

What do computational predictors say about ABTB2 p.Val741Ala (c.2222T>C)?

AlphaMissense predicts likely pathogenic (score 0.8048) — an in-silico prediction, not a clinical call.

ABTB2 p.Val741Ala

c.2222T>C · rs913188336 · VCV3133007

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8048 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0017%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8048	likely pathogenic
REVEL	0.517	indeterminate
SaProt	LLR -6.49	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 11	GERP 1.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 205 kb · p 0.0006 · regional, not allelic
Overall
CADD	25.4	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 0.0017% Admixed American · 1/58,810 alleles

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

Overall 0.000874% 14/1,601,458 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0017%	58,810
European (non-Finnish)	0.00111%	90,265

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.Val741Ala
Coding: c.2222T>C
MANE Select: NM_145804
dbSNP: rs913188336
Type: single nucleotide variant
Location: chr11:34161078 (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.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
ABTB2 p.Ala301Thr 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-val741ala (accessed [today's date]).

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