Is ABTB1 p.Arg130Cys (c.388C>T) pathogenic?

ABTB1 p.Arg130Cys (c.388C>T) is classified Uncertain significance in ABTB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-26). AlphaMissense: likely benign (0.2072); Very rare (popmax 0.00329%, sas).

How common is ABTB1 p.Arg130Cys (c.388C>T) in the general population?

ABTB1 p.Arg130Cys (c.388C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about ABTB1 p.Arg130Cys (c.388C>T)?

AlphaMissense predicts likely benign (score 0.2072) — an in-silico prediction, not a clinical call.

ABTB1 p.Arg130Cys

c.388C>T · rs149260862 · VCV2320156

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2072 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2072	likely benign
REVEL	0.796	moderately pathogenic-leaning
SaProt	LLR -11.90	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 7,290 bp · p 0.77 · 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 0.00329% South Asian · 3/91,086 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000684% 10/1,461,834 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,362
East Asian	0.00223%	44,874
European (non-Finnish)	0.000508%	196,668

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: ABTB1
Protein: p.Arg130Cys
Coding: c.388C>T
MANE Select: NM_172027
dbSNP: rs149260862
Type: single nucleotide variant
Location: chr3:127676339 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.59
Residue 130: the btb 1 domain

Full ABTB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABTB1 p.Ala165Ser Uncertain significance ★ ⚠ same type
ABTB1 p.Ala168Ser Uncertain significance ★ ⚠ same type
ABTB1 p.Ala216Pro Uncertain significance ★ ⚠ same type
ABTB1 p.Ala233Val Uncertain significance ★ ⚠ same type
ABTB1 p.Ala312Val Uncertain significance ★ ⚠ same type
ABTB1 p.Ala356Thr Uncertain significance ★ ⚠ same type
ABTB1 p.Ala373Thr Uncertain significance ★ ⚠ same type
ABTB1 p.Ala420Val 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/abtb1-p-arg130cys (accessed [today's date]).

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