Is ABTB1 p.Ser308Arg (c.924C>A) pathogenic?

ABTB1 p.Ser308Arg (c.924C>A) is classified Uncertain significance in ABTB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). AlphaMissense: likely benign (0.2377); Ultra-rare (popmax 0.0107%, nfe).

How common is ABTB1 p.Ser308Arg (c.924C>A) in the general population?

ABTB1 p.Ser308Arg (c.924C>A) is ultra-rare (popmax 0.0107%, nfe) (gnomAD).

What do computational predictors say about ABTB1 p.Ser308Arg (c.924C>A)?

AlphaMissense predicts likely benign (score 0.2377) — an in-silico prediction, not a clinical call.

ABTB1 p.Ser308Arg

c.924C>A · rs146406722 · VCV3132850

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2377 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2377	likely benign
REVEL	0.122	moderately benign-leaning
SaProt	LLR -7.83	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 -9.6	GERP -3.9
Regional constraint	o/e 0.99	unconstrained · MANE · 7,290 bp · p 0.77 · regional, not allelic
Overall
CADD	0.427	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 0.0107% European (non-Finnish) · 126/1,178,396 alleles

Filtering AF 0.00912% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00856%

Overall 0.00783% 126/1,610,094 alleles · ultra-rare

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.Ser308Arg
Coding: c.924C>A
MANE Select: NM_172027
dbSNP: rs146406722
Type: single nucleotide variant
Location: chr3:127677738 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.59
Residue 308: the btb 2 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-ser308arg (accessed [today's date]).

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