Is ANK2 p.Val1170= (c.3510A>G) pathogenic?

ANK2 p.Val1170= (c.3510A>G) is classified Benign in ANK2 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-02). Common (popmax 9.68%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Val1170= (c.3510A>G)?

ANK2 p.Val1170= (c.3510A>G) is associated with Cardiovascular phenotype, long QT syndrome, cardiac rhythm disease (ClinVar).

ANK2 p.Val1170=

Q: How common is ANK2 p.Val1170= (c.3510A>G) in the general population?

ANK2 p.Val1170= (c.3510A>G) is common (popmax 9.68%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3510A>G · rs35336373 · VCV35686

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 9.68%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.1	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP -5.4, phastCons 1
Overall
CADD	7.178	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.68% African / African-American · 7,264/75,004 alleles

Filtering AF 9.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.42%

Overall 0.553% 8,929/1,614,120 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.68%	10
Middle Eastern	0.858%	117
Admixed American	0.743%	135
Remaining individualsnot grpmax-eligible	0.738%	136
South Asian	0.448%	223
European (non-Finnish)	0.025%	4,000
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869

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.Val1170=
Coding: c.3510A>G
MANE Select: NM_001148
dbSNP: rs35336373
Type: single nucleotide variant
Location: chr4:113335976 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1170: a β-strand; the zu5 2 domain

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 cardiac rhythm disease cardiac arrhythmia, ankyrin-B-related

Similar variants

ANK2 p.Val1170Ile 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
ANK2 c.11032+11G>T Uncertain significance ★★ same condition
ANK2 c.11611-3T>A 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-val1170 (accessed [today's date]).

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