Is ANK2 p.Val2369Phe (c.7105G>T) pathogenic?

ANK2 p.Val2369Phe (c.7105G>T) is classified Conflicting classifications of pathogenicity in ANK2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-20). AlphaMissense: likely benign (0.0895); Ultra-rare (popmax 0.0986%, mid); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Val2369Phe (c.7105G>T)?

ANK2 p.Val2369Phe (c.7105G>T) is associated with Cardiovascular phenotype, long QT syndrome, dilated cardiomyopathy (ClinVar).

How common is ANK2 p.Val2369Phe (c.7105G>T) in the general population?

ANK2 p.Val2369Phe (c.7105G>T) is ultra-rare (popmax 0.0986%, mid) (gnomAD).

What do computational predictors say about ANK2 p.Val2369Phe (c.7105G>T)?

AlphaMissense predicts likely benign (score 0.0895) — an in-silico prediction, not a clinical call.

ANK2 p.Val2369Phe

c.7105G>T · rs758054052 · VCV238587

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0895 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0986%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0895	likely benign
REVEL	0.036	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 -0.031	GERP -5.4
Regional constraint	o/e 0.97	unconstrained · MANE · 28 kb · p 0.16 · regional, not allelic
Overall
CADD	0.992	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 0.0986% Middle Eastern · 6/6,084 alleles

Filtering AF 0.0429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.0124% 200/1,614,036 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0986%	1,014
European (non-Finnish)	0.0157%	6,378
Remaining individualsnot grpmax-eligible	0.0144%	6,943

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.Val2369Phe
Coding: c.7105G>T
MANE Select: NM_001148
dbSNP: rs758054052
Type: single nucleotide variant
Location: chr4:113355723 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2369: a UniProt-annotated variant site (in); the 'disordered' 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

Also linked: long QT syndrome dilated cardiomyopathy cardiac arrhythmia, ankyrin-B-related

Similar variants

ANK2 p.Val2369Ala Benign/Likely benign ★★ same residue
ANK2 p.Val2369Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
ANK2 p.Val2369Ser Uncertain significance ★ same residue
ANK2 p.Arg1007Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Arg1088Ter Pathogenic ★★ same condition
ANK2 p.Arg3113Ter Pathogenic ★★ same condition
ANK2 p.Arg895Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Arg977Ter Pathogenic ★★ 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-val2369phe (accessed [today's date]).

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