Is ANK3 p.Pro3866Ala (c.11596C>G) pathogenic?

ANK3 p.Pro3866Ala (c.11596C>G) is classified Uncertain significance in ANK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-12). AlphaMissense: likely pathogenic (0.8362); Absent from gnomAD v4.1.

How common is ANK3 p.Pro3866Ala (c.11596C>G) in the general population?

ANK3 p.Pro3866Ala (c.11596C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANK3 p.Pro3866Ala (c.11596C>G)?

AlphaMissense predicts likely pathogenic (score 0.8362) — an in-silico prediction, not a clinical call.

ANK3 p.Pro3866Ala

c.11596C>G · VCV3770048

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8362 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.8362	likely pathogenic
REVEL	0.276	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 12	GERP 5.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 1,310 bp · p 0.15 · regional, not allelic
Overall
CADD	23.7	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.Pro3866Ala
Coding: c.11596C>G
MANE Select: NM_020987
Type: single nucleotide variant
Location: chr10:60069285 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 (gnomAD)

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

Similar variants

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
ANK3 p.Ala2223Thr 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-pro3866ala (accessed [today's date]).

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