Is ANK3 p.Ala2820Pro (c.8458G>C) pathogenic?

ANK3 p.Ala2820Pro (c.8458G>C) is classified Uncertain significance in ANK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-01). AlphaMissense: likely benign (0.1131); Absent from gnomAD v4.1.

How common is ANK3 p.Ala2820Pro (c.8458G>C) in the general population?

ANK3 p.Ala2820Pro (c.8458G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANK3 p.Ala2820Pro (c.8458G>C)?

AlphaMissense predicts likely benign (score 0.1131) — an in-silico prediction, not a clinical call.

ANK3 p.Ala2820Pro

c.8458G>C · rs1452344286 · VCV623734

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1131 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1131	likely benign
REVEL	0.066	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.64	GERP 4.6
Regional constraint	o/e 0.92	unconstrained · MANE · 4,360 bp · p 0.0017 · regional, not allelic
Overall
CADD	16.1	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

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: ANK3
Protein: p.Ala2820Pro
Coding: c.8458G>C
MANE Select: NM_020987
dbSNP: rs1452344286
Type: single nucleotide variant
Location: chr10:60072423 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 (gnomAD)
Residue 2820: the 'disordered' region

Full ANK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANK3 p.Ala2820Thr Uncertain significance ★ ⚠ same residue
ANK3 c.2382+6C>T Uncertain significance ★★ same type
ANK3 p.Ala1461Thr Uncertain significance ★★ ⚠ same type
ANK3 p.Ala1534Val Uncertain significance ★★ same type
ANK3 p.Ala1630Val Uncertain significance ★★ ⚠ same type
ANK3 p.Ala169Thr Uncertain significance ★★ same type
ANK3 p.Ala2023Thr Uncertain significance ★★ ⚠ same type
ANK3 p.Ala218Thr 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/ank3-p-ala2820pro (accessed [today's date]).

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