Is ANK2 p.Pro2383Leu (c.7148C>T) pathogenic?

ANK2 p.Pro2383Leu (c.7148C>T) is classified Conflicting classifications of pathogenicity in ANK2 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-02-05). AlphaMissense: likely benign (0.0748); Ultra-rare (popmax 0.0533%, afr); Associated with long QT syndrome.

What condition is associated with ANK2 p.Pro2383Leu (c.7148C>T)?

ANK2 p.Pro2383Leu (c.7148C>T) is associated with long QT syndrome, cardiac arrhythmia, ankyrin-B-related (ClinVar).

How common is ANK2 p.Pro2383Leu (c.7148C>T) in the general population?

ANK2 p.Pro2383Leu (c.7148C>T) is ultra-rare (popmax 0.0533%, afr) (gnomAD).

What do computational predictors say about ANK2 p.Pro2383Leu (c.7148C>T)?

AlphaMissense predicts likely benign (score 0.0748) — an in-silico prediction, not a clinical call.

ANK2 p.Pro2383Leu

c.7148C>T · rs35960628 · VCV642356

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0748 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0533%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

long QT syndrome

Computational evidence

Protein change
AlphaMissense	0.0748	likely benign
REVEL	0.054	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.1	GERP -1.8
Regional constraint	o/e 0.97	unconstrained · MANE · 28 kb · p 0.16 · regional, not allelic
Overall
CADD	7.753	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 0.0533% African / African-American · 40/75,038 alleles

Filtering AF 0.0401% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0356%

Overall 0.00632% 102/1,614,088 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0533%	1,876
South Asian	0.0384%	2,602
Middle Eastern	0.0165%	6,062
Finnishnot grpmax-eligible	0.0125%	8,004
Remaining individualsnot grpmax-eligible	0.0112%	8,929
Admixed American	0.00833%	12,002
East Asian	0.00223%	44,870
European (non-Finnish)	0.000424%	235,995

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.Pro2383Leu
Coding: c.7148C>T
dbSNP: rs35960628
Type: single nucleotide variant
Location: chr4:113355766 (GRCh38)

Full ANK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

long QT syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiac arrhythmia, ankyrin-B-related

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-pro2383leu (accessed [today's date]).

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