Is ANK2 p.Ser575Arg (c.1725C>G) pathogenic?

ANK2 p.Ser575Arg (c.1725C>G) is classified Uncertain significance in ANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-06). AlphaMissense: likely pathogenic (0.7464); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Ser575Arg (c.1725C>G)?

ANK2 p.Ser575Arg (c.1725C>G) is associated with Cardiovascular phenotype (ClinVar).

How common is ANK2 p.Ser575Arg (c.1725C>G) in the general population?

ANK2 p.Ser575Arg (c.1725C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANK2 p.Ser575Arg (c.1725C>G)?

AlphaMissense predicts likely pathogenic (score 0.7464) — an in-silico prediction, not a clinical call.

ANK2 p.Ser575Arg

c.1725C>G · rs2153698530 · VCV3220963

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7464 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.7464	likely pathogenic
REVEL	0.409	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.81	GERP -0.29, phastCons 0.97
Regional constraint	o/e 0.77	unconstrained · MANE · 98 kb · p 4.4e-21 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ANK2
Protein: p.Ser575Arg
Coding: c.1725C>G
MANE Select: NM_001148
dbSNP: rs2153698530
Type: single nucleotide variant
Location: chr4:113277878 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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

Similar variants

ANK2 p.Ser575Gly Uncertain significance ★ same residue
ANK2 p.Ser575Ile 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

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-ser575arg (accessed [today's date]).

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