Is ABTB1 p.Ala216Pro (c.646G>C) pathogenic?

ABTB1 p.Ala216Pro (c.646G>C) is classified Uncertain significance in ABTB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-20). AlphaMissense: ambiguous (0.3527); Absent from gnomAD v4.1.

How common is ABTB1 p.Ala216Pro (c.646G>C) in the general population?

ABTB1 p.Ala216Pro (c.646G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABTB1 p.Ala216Pro (c.646G>C)?

AlphaMissense predicts ambiguous (score 0.3527) — an in-silico prediction, not a clinical call.

ABTB1 p.Ala216Pro

c.646G>C · rs1192887836 · VCV3132835

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3527 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3527	ambiguous
REVEL	0.251	benign-leaning
SaProt	LLR -14.76	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 7,290 bp · p 0.77 · regional, not allelic
Overall
CADD	19.45	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABTB1
Protein: p.Ala216Pro
Coding: c.646G>C
MANE Select: NM_172027
dbSNP: rs1192887836
Type: single nucleotide variant
Location: chr3:127677170 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.59

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

Similar variants

ABTB1 p.Ala216Val Likely benign ★ ⚠ same residue
ABTB1 p.Ala165Ser Uncertain significance ★ ⚠ same type
ABTB1 p.Ala168Ser 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-ala216pro (accessed [today's date]).

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