Is ANK2 p.Val2649= (c.7947C>T) pathogenic?

ANK2 p.Val2649= (c.7947C>T) is classified Benign/Likely benign in ANK2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-06). Ultra-rare (popmax 0.0646%, eas); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Val2649= (c.7947C>T)?

ANK2 p.Val2649= (c.7947C>T) is associated with Cardiovascular phenotype, long QT syndrome (ClinVar).

How common is ANK2 p.Val2649= (c.7947C>T) in the general population?

ANK2 p.Val2649= (c.7947C>T) is ultra-rare (popmax 0.0646%, eas) (gnomAD).

ANK2 p.Val2649=

c.7947C>T · rs148649499 · VCV2913794

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0646%, eas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.24	GERP -1.1
Overall
CADD	0.692	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0646% East Asian · 29/44,874 alleles

Filtering AF 0.0461% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.04%

Overall 0.00186% 30/1,614,060 alleles · ultra-rare exomes 21/1,461,802 · genomes 9/152,258 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0646%	1,547
Remaining individualsnot grpmax-eligible	0.0016%	62,504

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.Val2649=
Coding: c.7947C>T
MANE Select: NM_001148
dbSNP: rs148649499
Type: single nucleotide variant
Location: chr4:113356565 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2649: 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

Similar variants

ANK2 p.Val2649Ile Uncertain significance ★ ⚠ 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 c.2278-3C>T 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-val2649 (accessed [today's date]).

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