Is ANK2 p.Arg1007Gln (c.3020G>A) pathogenic?

ANK2 p.Arg1007Gln (c.3020G>A) is classified Uncertain significance in ANK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-13). AlphaMissense: likely pathogenic (0.9833); Very rare (popmax 0.0011%, sas); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Arg1007Gln (c.3020G>A)?

ANK2 p.Arg1007Gln (c.3020G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is ANK2 p.Arg1007Gln (c.3020G>A) in the general population?

ANK2 p.Arg1007Gln (c.3020G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ANK2 p.Arg1007Gln (c.3020G>A)?

AlphaMissense predicts likely pathogenic (score 0.9833) — an in-silico prediction, not a clinical call.

ANK2 p.Arg1007Gln

c.3020G>A · rs1554509161 · VCV518604

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9833 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9833	likely pathogenic · top 10% in ANK2
REVEL	0.61	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 98 kb · p 4.4e-21 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,072 alleles

Overall 0.000124% 2/1,614,160 alleles · very rare exomes 2/1,461,866 · genomes 0/152,294 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,072
European (non-Finnish)	8.47e-05%	1,180,026

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.Arg1007Gln
Coding: c.3020G>A
MANE Select: NM_001148
dbSNP: rs1554509161
Type: single nucleotide variant
Location: chr4:113330365 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1007: a β-strand; the zu5 1 domain; the 'interaction with sptbn1' region

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANK2 p.Arg1007Ter Pathogenic/Likely pathogenic ★★ same residue
ANK2 p.Arg3113Ter Pathogenic ★★ same condition
ANK2 p.Arg895Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Arg977Ter Pathogenic ★★ same condition
ANK2 c.11611-3T>A Uncertain significance ★★ same condition
ANK2 c.1783-3C>T Uncertain significance ★★ same condition
ANK2 c.2079+5T>G Uncertain significance ★★ same condition
ANK2 p.Ala1152Val 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-arg1007gln (accessed [today's date]).

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