Is ANK2 p.Cys60Ter (c.180C>A) pathogenic?

ANK2 p.Cys60Ter (c.180C>A) is classified Uncertain significance in ANK2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2026-06-18). Absent from gnomAD v4.1; Associated with complex neurodevelopmental disorder.

What condition is associated with ANK2 p.Cys60Ter (c.180C>A)?

ANK2 p.Cys60Ter (c.180C>A) is associated with complex neurodevelopmental disorder (ClinVar).

How common is ANK2 p.Cys60Ter (c.180C>A) in the general population?

ANK2 p.Cys60Ter (c.180C>A) 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.

ANK2 p.Cys60Ter

c.180C>A · VCV4879446

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

complex neurodevelopmental disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 46
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.72, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

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

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.Cys60Ter
Coding: c.180C>A
MANE Select: NM_001148
Type: single nucleotide variant
Location: chr4:113174511 (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.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.Phe1401fs Likely pathogenic ★ 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-cys60ter (accessed [today's date]).

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