Is ANK3 p.Ala2006Val (c.6017C>T) pathogenic?

ANK3 p.Ala2006Val (c.6017C>T) is classified Conflicting classifications of pathogenicity in ANK3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-29). AlphaMissense: likely benign (0.0716); Ultra-rare (popmax 0.0184%, amr); Associated with Inborn genetic diseases.

What condition is associated with ANK3 p.Ala2006Val (c.6017C>T)?

ANK3 p.Ala2006Val (c.6017C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ANK3 p.Ala2006Val (c.6017C>T) in the general population?

ANK3 p.Ala2006Val (c.6017C>T) is ultra-rare (popmax 0.0184%, amr) (gnomAD).

What do computational predictors say about ANK3 p.Ala2006Val (c.6017C>T)?

AlphaMissense predicts likely benign (score 0.0716) — an in-silico prediction, not a clinical call.

ANK3 p.Ala2006Val

c.6017C>T · rs202232309 · VCV2065101

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0716 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0184%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0716	likely benign
REVEL	0.174	moderately 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 -0.31	GERP -2
Regional constraint	o/e 0.86	unconstrained · MANE · 7,641 bp · p 6.9e-05 · regional, not allelic
Overall
CADD	3.347	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 0.0184% Admixed American · 11/59,934 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00786%

Overall 0.00855% 138/1,613,588 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0266%	3,765
Admixed Americangrpmax	0.0184%	5,449
East Asian	0.0178%	5,610
Middle Eastern	0.0165%	6,052
Remaining individualsnot grpmax-eligible	0.0144%	6,942
European (non-Finnish)	0.00712%	14,046
African / African-American	0.00667%	14,999
South Asian	0.0033%	30,301

Finnish 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: ANK3
Protein: p.Ala2006Val
Coding: c.6017C>T
MANE Select: NM_020987
dbSNP: rs202232309
Type: single nucleotide variant
Location: chr10:60074864 (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.Ala2006= Likely benign ★ 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-ala2006val (accessed [today's date]).

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