Is ANK2 p.Phe1313Leu (c.3937T>C) pathogenic?

ANK2 p.Phe1313Leu (c.3937T>C) is classified Uncertain significance in ANK2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-18). AlphaMissense: likely pathogenic (0.9525); Absent from gnomAD v4.1; Associated with long QT syndrome.

What condition is associated with ANK2 p.Phe1313Leu (c.3937T>C)?

ANK2 p.Phe1313Leu (c.3937T>C) is associated with long QT syndrome (ClinVar).

How common is ANK2 p.Phe1313Leu (c.3937T>C) in the general population?

ANK2 p.Phe1313Leu (c.3937T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANK2 p.Phe1313Leu (c.3937T>C)?

AlphaMissense predicts likely pathogenic (score 0.9525) — an in-silico prediction, not a clinical call.

ANK2 p.Phe1313Leu

c.3937T>C · rs2094326229 · VCV1977968

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9525 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

long QT syndrome

Computational evidence

Protein change
AlphaMissense	0.9525	likely pathogenic
REVEL	0.209	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 98 kb · p 4.4e-21 · regional, not allelic
Overall
CADD	26.9	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

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.Phe1313Leu
Coding: c.3937T>C
MANE Select: NM_001148
dbSNP: rs2094326229
Type: single nucleotide variant
Location: chr4:113341731 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1313: an α-helix; the 'upa domain' region

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

Similar variants

ANK2 p.Arg3113Ter 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
ANK2 c.3125+6G>A Uncertain significance ★★ same condition
ANK2 c.693+6G>A Uncertain significance ★★ same condition
ANK2 c.85-3C>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-phe1313leu (accessed [today's date]).

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