Is ANK2 p.Pro1950= (c.5850T>C) pathogenic?

ANK2 p.Pro1950= (c.5850T>C) is classified Likely benign in ANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-23). Very rare (popmax 0.000339%, nfe); Associated with long QT syndrome.

What condition is associated with ANK2 p.Pro1950= (c.5850T>C)?

ANK2 p.Pro1950= (c.5850T>C) is associated with long QT syndrome (ClinVar).

How common is ANK2 p.Pro1950= (c.5850T>C) in the general population?

ANK2 p.Pro1950= (c.5850T>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

ANK2 p.Pro1950=

c.5850T>C · rs974482179 · VCV2997199

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

long QT syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -4.4	GERP -5.2
Overall
CADD	0.333	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,950 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,906 alleles · very rare exomes 4/1,461,832 · genomes 0/152,074 · joint denominator

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.Pro1950=
Coding: c.5850T>C
MANE Select: NM_001148
dbSNP: rs974482179
Type: single nucleotide variant
Location: chr4:113354468 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1950: the 'disordered' region; the 'repeat-rich region' 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.Pro1950His Uncertain significance ★ ⚠ same residue
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

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-pro1950 (accessed [today's date]).

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