Is ANK2 p.Val2708= (c.8124A>G) pathogenic?

ANK2 p.Val2708= (c.8124A>G) is classified Likely benign in ANK2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0198%, nfe); Associated with long QT syndrome.

What condition is associated with ANK2 p.Val2708= (c.8124A>G)?

ANK2 p.Val2708= (c.8124A>G) is associated with long QT syndrome, cardiac arrhythmia, ankyrin-B-related (ClinVar).

How common is ANK2 p.Val2708= (c.8124A>G) in the general population?

ANK2 p.Val2708= (c.8124A>G) is ultra-rare (popmax 0.0198%, nfe) (gnomAD).

ANK2 p.Val2708=

c.8124A>G · rs776586126 · VCV513345

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0198%, nfe)

Conditions

long QT syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.75	GERP -5.4
Overall
CADD	1.66	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0198% European (non-Finnish) · 234/1,179,994 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0169%

Overall 0.0154% 249/1,614,032 alleles · ultra-rare exomes 240/1,461,818 · genomes 9/152,214 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0198%	5,043
Remaining individualsnot grpmax-eligible	0.0176%	5,680
African / African-American	0.00267%	37,468
Admixed American	0.00167%	60,002
Finnishnot grpmax-eligible	0.00156%	64,044

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.Val2708=
Coding: c.8124A>G
MANE Select: NM_001148
dbSNP: rs776586126
Type: single nucleotide variant
Location: chr4:113356742 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2708: the 'disordered' region

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

Disease context

long QT syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiac arrhythmia, ankyrin-B-related

Similar variants

ANK2 p.Val2708Ala Likely pathogenic ⚠ same residue
ANK2 p.Arg1007Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Arg1088Ter Pathogenic ★★ same condition
ANK2 p.Arg3113Ter Pathogenic ★★ same condition
ANK2 c.11032+11G>T Uncertain significance ★★ 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

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-val2708 (accessed [today's date]).

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