Is ANK3 p.Arg2284Gln (c.6851G>A) pathogenic?

ANK3 p.Arg2284Gln (c.6851G>A) is classified Conflicting classifications of pathogenicity in ANK3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-30). AlphaMissense: ambiguous (0.4276); Ultra-rare (popmax 0.03%, amr); Associated with Inborn genetic diseases.

What condition is associated with ANK3 p.Arg2284Gln (c.6851G>A)?

ANK3 p.Arg2284Gln (c.6851G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ANK3 p.Arg2284Gln (c.6851G>A) in the general population?

ANK3 p.Arg2284Gln (c.6851G>A) is ultra-rare (popmax 0.03%, amr) (gnomAD).

What do computational predictors say about ANK3 p.Arg2284Gln (c.6851G>A)?

AlphaMissense predicts ambiguous (score 0.4276) — an in-silico prediction, not a clinical call.

ANK3 p.Arg2284Gln

c.6851G>A · rs767414907 · VCV2158271

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4276 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4276	ambiguous
REVEL	0.176	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 4.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 4,360 bp · p 0.0017 · regional, not allelic
Overall
CADD	25.0	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 0.03% Admixed American · 18/59,998 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.00186% 30/1,613,936 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.03%	3,333
East Asian	0.00223%	44,868
African / African-American	0.00134%	74,896
South Asian	0.0011%	91,072
European (non-Finnish)	0.000763%	131,111

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.Arg2284Gln
Coding: c.6851G>A
MANE Select: NM_020987
dbSNP: rs767414907
Type: single nucleotide variant
Location: chr10:60074030 (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.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
ANK3 p.Arg1623Gln 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-arg2284gln (accessed [today's date]).

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