Is ANK2 p.Ala2336Val (c.7007C>T) pathogenic?

ANK2 p.Ala2336Val (c.7007C>T) is classified Benign in ANK2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.1048); Common (popmax 5.23%, afr) — too common for a highly-penetrant pathogenic allele; Associated with long QT syndrome.

What condition is associated with ANK2 p.Ala2336Val (c.7007C>T)?

ANK2 p.Ala2336Val (c.7007C>T) is associated with long QT syndrome, cardiac arrhythmia, ankyrin-B-related (ClinVar).

What do computational predictors say about ANK2 p.Ala2336Val (c.7007C>T)?

AlphaMissense predicts likely benign (score 0.1048) — an in-silico prediction, not a clinical call.

ANK2 p.Ala2336Val

Q: How common is ANK2 p.Ala2336Val (c.7007C>T) in the general population?

ANK2 p.Ala2336Val (c.7007C>T) is common (popmax 5.23%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.7007C>T · rs61734477 · VCV191559

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.1048 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.23%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

long QT syndrome

Computational evidence

Protein change
AlphaMissense	0.1048	likely benign
REVEL	0.049	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 -0.12	GERP -0.52
Regional constraint	o/e 0.97	unconstrained · MANE · 28 kb · p 0.16 · regional, not allelic
Overall
CADD	5.432	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.23% African / African-American · 3,920/75,006 alleles

Filtering AF 5.09% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.03%

Overall 0.31% 5,009/1,614,000 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.23%	19
Admixed American	0.433%	231
Remaining individualsnot grpmax-eligible	0.379%	264
Middle Eastern	0.347%	288
European (non-Finnish)	0.0456%	2,193
South Asian	0.034%	2,938
Finnishnot grpmax-eligible	0.00312%	32,014

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.Ala2336Val
Coding: c.7007C>T
MANE Select: NM_001148
dbSNP: rs61734477
Type: single nucleotide variant
Location: chr4:113355625 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2336: 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.Ala2336Thr Conflicting classifications of pathogenicity ★ ⚠ 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-ala2336val (accessed [today's date]).

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