Is ANK2 p.Arg3602Ter (c.10804C>T) pathogenic?

ANK2 p.Arg3602Ter (c.10804C>T) is classified Uncertain significance in ANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-20). Very rare (popmax 0.000254%, nfe); Associated with ANK2-related disorder.

What condition is associated with ANK2 p.Arg3602Ter (c.10804C>T)?

ANK2 p.Arg3602Ter (c.10804C>T) is associated with ANK2-related disorder (ClinVar).

How common is ANK2 p.Arg3602Ter (c.10804C>T) in the general population?

ANK2 p.Arg3602Ter (c.10804C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

ANK2 p.Arg3602Ter

c.10804C>T · VCV4854696

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

ANK2-related 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 40 of 46
REVEL	0.133	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Overall
CADD	46.0	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

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,584 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,613,350 alleles · very rare exomes 4/1,461,094 · genomes 0/152,256 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,458
European (non-Finnish)grpmax	0.000254%	393,195

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ANK2
Protein: p.Arg3602Ter
Coding: c.10804C>T
MANE Select: NM_001148
Type: single nucleotide variant
Location: chr4:113363385 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 3602: an α-helix; the death 2 domain

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

Disease context

ANK2-related disorder

Similar variants

ANK2 p.Arg3602Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ANK2 p.Arg3602Leu Uncertain significance ★ ⚠ same residue
ANK2 p.Arg1088Ter Pathogenic ★★ same condition
ANK2 p.Arg888Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 c.85-28508A>G Uncertain significance ★★ same condition
ANK2 c.85-57022A>C Uncertain significance ★★ same condition
ANK2 p.Ala41Thr Uncertain significance ★★ ⚠ same condition
ANK2 p.Gln2672His 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-arg3602ter (accessed [today's date]).

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