Is ANK3 p.Arg709Gln (c.2126G>A) pathogenic?

ANK3 p.Arg709Gln (c.2126G>A) is classified Uncertain significance in ANK3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-04-28). AlphaMissense: likely benign (0.1433); Very rare (popmax 0.01%, amr); Associated with Inborn genetic diseases.

What condition is associated with ANK3 p.Arg709Gln (c.2126G>A)?

ANK3 p.Arg709Gln (c.2126G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ANK3 p.Arg709Gln (c.2126G>A) in the general population?

ANK3 p.Arg709Gln (c.2126G>A) is very rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about ANK3 p.Arg709Gln (c.2126G>A)?

AlphaMissense predicts likely benign (score 0.1433) — an in-silico prediction, not a clinical call.

ANK3 p.Arg709Gln

c.2126G>A · rs755310927 · VCV1425026

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1433 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1433	likely benign
REVEL	0.251	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 2.5, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 105 kb · p 5.9e-15 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/60,002 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000867% 14/1,614,062 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,000
East Asian	0.00223%	44,896
South Asian	0.0022%	45,543
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-American	0.00133%	74,942
European (non-Finnish)	0.000254%	393,345

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: ANK3
Protein: p.Arg709Gln
Coding: c.2126G>A
MANE Select: NM_020987
dbSNP: rs755310927
Type: single nucleotide variant
Location: chr10:60181387 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 (gnomAD)

Full ANK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANK3 p.Arg709Ter Likely pathogenic ★ same residue
ANK3 p.Ala1534Val Uncertain significance ★★ same condition
ANK3 p.Ala218Thr Uncertain significance ★★ same condition
ANK3 p.Ala259Thr Uncertain significance ★★ same condition
ANK3 p.Ala324Gly Uncertain significance ★★ ⚠ same condition
ANK3 p.Ala3262Val Uncertain significance ★★ ⚠ same condition
ANK3 p.Ala540Thr Uncertain significance ★★ same condition
ANK3 p.Arg1012Cys 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/ank3-p-arg709gln (accessed [today's date]).

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