Is ANK3 p.Pro2082Ala (c.6244C>G) pathogenic?

ANK3 p.Pro2082Ala (c.6244C>G) is classified Uncertain significance in ANK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely pathogenic (0.6572); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ANK3 p.Pro2082Ala (c.6244C>G)?

ANK3 p.Pro2082Ala (c.6244C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ANK3 p.Pro2082Ala (c.6244C>G) in the general population?

ANK3 p.Pro2082Ala (c.6244C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANK3 p.Pro2082Ala (c.6244C>G)?

AlphaMissense predicts likely pathogenic (score 0.6572) — an in-silico prediction, not a clinical call.

ANK3 p.Pro2082Ala

c.6244C>G · VCV4835251

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6572 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6572	likely pathogenic
REVEL	0.265	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 5.4, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 7,641 bp · p 6.9e-05 · regional, not allelic
Overall
CADD	24.8	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: ANK3
Protein: p.Pro2082Ala
Coding: c.6244C>G
MANE Select: NM_020987
Type: single nucleotide variant
Location: chr10:60074637 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 (gnomAD)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANK3 p.Ala1534Val Uncertain significance ★★ same condition
ANK3 p.Ala218Thr Uncertain significance ★★ same condition
ANK3 p.Ala259Thr Uncertain significance ★★ same condition
ANK3 p.Ala324Gly Uncertain significance ★★ ⚠ same condition
ANK3 p.Ala3262Val Uncertain significance ★★ ⚠ same condition
ANK3 p.Ala540Thr Uncertain significance ★★ same condition
ANK3 p.Arg1012Cys Uncertain significance ★★ same condition
ANK3 p.Arg1623Gln Uncertain significance ★★ same condition

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-pro2082ala (accessed [today's date]).

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