Is ANK2 p.Ser1979Leu (c.5936C>T) pathogenic?

ANK2 p.Ser1979Leu (c.5936C>T) is classified Benign/Likely benign in ANK2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-11-30). AlphaMissense: ambiguous (0.3899); Rare (popmax 0.355%, sas); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Ser1979Leu (c.5936C>T)?

ANK2 p.Ser1979Leu (c.5936C>T) is associated with Cardiovascular phenotype, long QT syndrome, cardiac arrhythmia, ankyrin-B-related (ClinVar).

How common is ANK2 p.Ser1979Leu (c.5936C>T) in the general population?

ANK2 p.Ser1979Leu (c.5936C>T) is rare (popmax 0.355%, sas) (gnomAD).

What do computational predictors say about ANK2 p.Ser1979Leu (c.5936C>T)?

AlphaMissense predicts ambiguous (score 0.3899) — an in-silico prediction, not a clinical call.

ANK2 p.Ser1979Leu

c.5936C>T · rs531574502 · VCV347327

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.3899 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.355%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.3899	ambiguous
REVEL	0.061	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 1.9, phastCons 0.99
Regional constraint	o/e 0.97	unconstrained · MANE · 28 kb · p 0.16 · regional, not allelic
Overall
CADD	23.2	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 0.355% South Asian · 323/91,072 alleles

Filtering AF 0.323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.31%

Overall 0.023% 372/1,614,094 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.355%	282
Remaining individualsnot grpmax-eligible	0.0176%	5,682
African / African-American	0.00533%	18,758
European (non-Finnish)	0.00288%	34,705

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.Ser1979Leu
Coding: c.5936C>T
MANE Select: NM_001148
dbSNP: rs531574502
Type: single nucleotide variant
Location: chr4:113354554 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1979: 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.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
ANK2 c.1783-3C>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-ser1979leu (accessed [today's date]).

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