Is ANK2 p.Asp2199Asn (c.6595G>A) pathogenic?

ANK2 p.Asp2199Asn (c.6595G>A) is classified Uncertain significance in ANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-26). AlphaMissense: likely benign (0.1163); Very rare (popmax 0.000508%, nfe).

How common is ANK2 p.Asp2199Asn (c.6595G>A) in the general population?

ANK2 p.Asp2199Asn (c.6595G>A) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about ANK2 p.Asp2199Asn (c.6595G>A)?

AlphaMissense predicts likely benign (score 0.1163) — an in-silico prediction, not a clinical call.

ANK2 p.Asp2199Asn

c.6595G>A · VCV4968303

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1163 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1163	likely benign
REVEL	0.108	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 0.033, phastCons 0.95
Regional constraint	o/e 0.97	unconstrained · MANE · 28 kb · p 0.16 · regional, not allelic
Overall
CADD	17.64	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000508% European (non-Finnish) · 6/1,179,990 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,614,034 alleles · very rare

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.Asp2199Asn
Coding: c.6595G>A
MANE Select: NM_001148
Type: single nucleotide variant
Location: chr4:113355213 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2199: the 'disordered' region

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

Similar variants

ANK2 p.Asp2199His Uncertain significance ★★ ⚠ 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
ANK2 c.11032+11G>T Uncertain significance ★★ 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-asp2199asn (accessed [today's date]).

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