Is ANK2 p.Thr697Arg (c.2090C>G) pathogenic?

ANK2 p.Thr697Arg (c.2090C>G) is classified Uncertain significance in ANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-13). AlphaMissense: likely pathogenic (0.8278); Absent from gnomAD v4.1; Associated with complex neurodevelopmental disorder.

What condition is associated with ANK2 p.Thr697Arg (c.2090C>G)?

ANK2 p.Thr697Arg (c.2090C>G) is associated with complex neurodevelopmental disorder (ClinVar).

How common is ANK2 p.Thr697Arg (c.2090C>G) in the general population?

ANK2 p.Thr697Arg (c.2090C>G) is absent from gnomAD v4.1 (gnomAD).

How is Non-specific syndromic intellectual disability inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ANK2 p.Thr697Arg (c.2090C>G)?

AlphaMissense predicts likely pathogenic (score 0.8278) — an in-silico prediction, not a clinical call.

ANK2 p.Thr697Arg

c.2090C>G · VCV3600426

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8278 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

complex neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.8278	likely pathogenic
REVEL	0.718	pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 98 kb · p 4.4e-21 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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: ANK2
Protein: p.Thr697Arg
Coding: c.2090C>G
MANE Select: NM_001148
Type: single nucleotide variant
Location: chr4:113287615 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

Full ANK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

complex neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Non-specific syndromic intellectual disability (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Childhood, Infancy

Similar variants

ANK2 p.Thr697= Likely benign ★★ same residue
ANK2 p.Ala2754Val Uncertain significance ★★ ⚠ same condition
ANK2 p.Asn795Thr Uncertain significance ★★ ⚠ same condition
ANK2 p.Cys3244Arg Uncertain significance ★★ ⚠ same condition
ANK2 p.Gly673Val Uncertain significance ★★ ⚠ same condition
ANK2 p.Thr2271Ile Uncertain significance ★★ ⚠ same condition
ANK2 p.Asp676Val Conflicting classifications of pathogenicity ★ same condition
ANK2 p.Cys60Ter 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/ank2-p-thr697arg (accessed [today's date]).

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