Is ANK2 p.Val2971Ile (c.8911G>A) pathogenic?

ANK2 p.Val2971Ile (c.8911G>A) is classified Benign/Likely benign in ANK2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-23). AlphaMissense: likely benign (0.0687); Ultra-rare (popmax 0.0274%, sas); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Val2971Ile (c.8911G>A)?

ANK2 p.Val2971Ile (c.8911G>A) is associated with Cardiovascular phenotype, long QT syndrome (ClinVar).

How common is ANK2 p.Val2971Ile (c.8911G>A) in the general population?

ANK2 p.Val2971Ile (c.8911G>A) is ultra-rare (popmax 0.0274%, sas) (gnomAD).

What do computational predictors say about ANK2 p.Val2971Ile (c.8911G>A)?

AlphaMissense predicts likely benign (score 0.0687) — an in-silico prediction, not a clinical call.

ANK2 p.Val2971Ile

c.8911G>A · rs752493662 · VCV863768

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0687 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0274%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0687	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.11	GERP -1.2
Regional constraint	o/e 0.97	unconstrained · MANE · 28 kb · p 0.16 · regional, not allelic
Overall
CADD	3.184	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0274% South Asian · 25/91,088 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0163%

Overall 0.0052% 84/1,613,934 alleles · ultra-rare exomes 79/1,461,810 · genomes 5/152,124 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0274%	3,644
East Asian	0.0134%	7,482
Remaining individualsnot grpmax-eligible	0.0096%	10,413
European (non-Finnish)	0.00398%	25,105

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.Val2971Ile
Coding: c.8911G>A
MANE Select: NM_001148
dbSNP: rs752493662
Type: single nucleotide variant
Location: chr4:113357529 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: long QT syndrome

Similar variants

ANK2 p.Val2971Ala Uncertain significance ★ ⚠ same residue
ANK2 p.Val2971= Likely benign ★ same residue
ANK2 p.Val2971Leu Uncertain significance ★ ⚠ same residue
ANK2 p.Arg3113Ter Pathogenic ★★ same condition
ANK2 p.Arg895Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Arg977Ter Pathogenic ★★ 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-val2971ile (accessed [today's date]).

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