Is ANK2 p.Phe1401fs (c.4203del) pathogenic?

ANK2 p.Phe1401fs (c.4203del) is classified Likely pathogenic in ANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-31). Absent from gnomAD; Associated with complex neurodevelopmental disorder.

What condition is associated with ANK2 p.Phe1401fs (c.4203del)?

ANK2 p.Phe1401fs (c.4203del) is associated with complex neurodevelopmental disorder (ClinVar).

How common is ANK2 p.Phe1401fs (c.4203del) in the general population?

ANK2 p.Phe1401fs (c.4203del) is absent from gnomAD (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.

ANK2 p.Phe1401fs

c.4203del · rs2504036153 · VCV2672177

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

complex neurodevelopmental disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 34 of 46
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ANK2
Protein: p.Phe1401fs
Coding: c.4203del
MANE Select: NM_001148
dbSNP: rs2504036153
Type: Deletion
Location: chr4:113343097 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1401: a β-strand; the 'upa domain' region

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.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.Thr697Arg Uncertain significance ★ ⚠ 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-phe1401fs (accessed [today's date]).

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