Is ANK2 p.Arg473Ter (c.1417C>T) pathogenic?

ANK2 p.Arg473Ter (c.1417C>T) is classified Likely pathogenic in ANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-21). Absent from gnomAD v4.1.

How common is ANK2 p.Arg473Ter (c.1417C>T) in the general population?

ANK2 p.Arg473Ter (c.1417C>T) is absent from gnomAD v4.1 (gnomAD).

ANK2 p.Arg473Ter

c.1417C>T · rs864622760 · VCV2446019

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,567,708)

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 14 of 46
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.26	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 4.9	GERP 2.5, phastCons 1
Overall
CADD	40.0	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

No allele count reported in gnomAD v4.1 (AN 1,567,708). 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.Arg473Ter
Coding: c.1417C>T
MANE Select: NM_001148
dbSNP: rs864622760
Type: single nucleotide variant
Location: chr4:113264927 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 473: an α-helix

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

Similar variants

ANK2 p.Arg473Gln Uncertain significance ★★ same residue
ANK2 p.Arg473= Likely benign ★ same residue
ANK2 p.Arg1007Ter Pathogenic/Likely pathogenic ★★ same type
ANK2 p.Arg1088Ter Pathogenic ★★ same type
ANK2 p.Arg3113Ter Pathogenic ★★ same type
ANK2 p.Arg888Ter Pathogenic/Likely pathogenic ★★ same type
ANK2 p.Arg895Ter Pathogenic/Likely pathogenic ★★ same type
ANK2 p.Arg977Ter Pathogenic ★★ 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/ank2-p-arg473ter (accessed [today's date]).

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