Is ANK2 p.Asp905Asn (c.2713G>A) pathogenic?

ANK2 p.Asp905Asn (c.2713G>A) is classified Uncertain significance in ANK2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-10-20). AlphaMissense: ambiguous (0.4851); Very rare (popmax 0.00439%, sas); Associated with long QT syndrome.

What condition is associated with ANK2 p.Asp905Asn (c.2713G>A)?

ANK2 p.Asp905Asn (c.2713G>A) is associated with long QT syndrome (ClinVar).

How common is ANK2 p.Asp905Asn (c.2713G>A) in the general population?

ANK2 p.Asp905Asn (c.2713G>A) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about ANK2 p.Asp905Asn (c.2713G>A)?

AlphaMissense predicts ambiguous (score 0.4851) — an in-silico prediction, not a clinical call.

ANK2 p.Asp905Asn

c.2713G>A · rs759275920 · VCV190596

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4851 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Conditions

long QT syndrome

Computational evidence

Protein change
AlphaMissense	0.4851	ambiguous
REVEL	0.345	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.29 · evaluated, not missing
Pangolin	Δ0.20	gain · loss 0.03 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 98 kb · p 4.4e-21 · regional, not allelic
Overall
CADD	33.0	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 0.00439% South Asian · 4/91,048 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00167% 27/1,613,784 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,802
South Asiangrpmax	0.00439%	22,762
European (non-Finnish)	0.00161%	62,103
Remaining individualsnot grpmax-eligible	0.0016%	62,472
African / African-American	0.00134%	74,878

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp905Asn
Coding: c.2713G>A
MANE Select: NM_001148
dbSNP: rs759275920
Type: single nucleotide variant
Location: chr4:113317726 (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

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

Similar variants

ANK2 p.Asp905Glu 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-asp905asn (accessed [today's date]).

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