Is ANK3 p.Arg1012Cys (c.3034C>T) pathogenic?

ANK3 p.Arg1012Cys (c.3034C>T) is classified Uncertain significance in ANK3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-31). AlphaMissense: likely pathogenic (0.9532); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ANK3 p.Arg1012Cys (c.3034C>T)?

ANK3 p.Arg1012Cys (c.3034C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ANK3 p.Arg1012Cys (c.3034C>T) in the general population?

ANK3 p.Arg1012Cys (c.3034C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ANK3 p.Arg1012Cys (c.3034C>T)?

AlphaMissense predicts likely pathogenic (score 0.9532) — an in-silico prediction, not a clinical call.

ANK3 p.Arg1012Cys

c.3034C>T · rs2132095747 · VCV2363573

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9532 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9532	likely pathogenic
REVEL	0.522	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.81 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 6.5, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 105 kb · p 5.9e-15 · 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 8.47e-05% European (non-Finnish) · 1/1,179,966 alleles

Overall 0.000657% 1/152,178 alleles · very rare

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.Arg1012Cys
Coding: c.3034C>T
MANE Select: NM_020987
dbSNP: rs2132095747
Type: single nucleotide variant
Location: chr10:60108969 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 (gnomAD)
Residue 1012: the zu5 1 domain

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.Arg1623Gln Uncertain significance ★★ same condition
ANK3 p.Arg2367Gln 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-arg1012cys (accessed [today's date]).

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