Is ANK2 p.Ser1905= (c.5715G>A) pathogenic?

ANK2 p.Ser1905= (c.5715G>A) is classified Benign in ANK2 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2025-12-07). Low-frequency (popmax 2.28%, sas); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Ser1905= (c.5715G>A)?

ANK2 p.Ser1905= (c.5715G>A) is associated with Cardiovascular phenotype, long QT syndrome, cardiac arrhythmia, ankyrin-B-related (ClinVar).

How common is ANK2 p.Ser1905= (c.5715G>A) in the general population?

ANK2 p.Ser1905= (c.5715G>A) is low-frequency (popmax 2.28%, sas) (gnomAD).

ANK2 p.Ser1905=

c.5715G>A · rs143404578 · VCV35689

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.28%, sas)

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 -6.3	GERP -5.7
Overall
CADD	0.207	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.28% South Asian · 2,075/91,082 alleles

Filtering AF 2.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.16%

Overall 0.14% 2,263/1,614,016 alleles · low-frequency exomes 2,115/1,461,834 · genomes 148/152,182 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	2.28%	44
Remaining individualsnot grpmax-eligible	0.162%	619
Middle Eastern	0.132%	758
African / African-American	0.008%	12,499
European (non-Finnish)	0.0061%	16,389
Finnishnot grpmax-eligible	0.00156%	63,998

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.Ser1905=
Coding: c.5715G>A
MANE Select: NM_001148
dbSNP: rs143404578
Type: single nucleotide variant
Location: chr4:113354333 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1905: the 'disordered' region; the 'repeat-rich region' 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 cardiac arrhythmia, ankyrin-B-related

Similar variants

ANK2 p.Ser1905Leu 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-ser1905 (accessed [today's date]).

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