Is ANK3 p.Ala2004Val (c.6011C>T) pathogenic?

ANK3 p.Ala2004Val (c.6011C>T) is classified Benign in ANK3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.0898); Low-frequency (popmax 1.85%, afr).

How common is ANK3 p.Ala2004Val (c.6011C>T) in the general population?

ANK3 p.Ala2004Val (c.6011C>T) is low-frequency (popmax 1.85%, afr) (gnomAD).

What do computational predictors say about ANK3 p.Ala2004Val (c.6011C>T)?

AlphaMissense predicts likely benign (score 0.0898) — an in-silico prediction, not a clinical call.

ANK3 p.Ala2004Val

c.6011C>T · rs76855192 · VCV726790

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0898 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.85%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0898	likely benign
REVEL	0.074	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 8.1	GERP 4.7, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 7,641 bp · p 6.9e-05 · regional, not allelic
Overall
CADD	21.4	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 1.85% African / African-American · 1,391/75,026 alleles

Filtering AF 1.77% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.74%

Overall 0.0949% 1,531/1,613,778 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.85%	54
Admixed American	0.0984%	1,017
Remaining individualsnot grpmax-eligible	0.0976%	1,024
Middle Eastern	0.0496%	2,018
South Asian	0.0044%	22,730
European (non-Finnish)	0.0011%	90,764

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.Ala2004Val
Coding: c.6011C>T
MANE Select: NM_020987
dbSNP: rs76855192
Type: single nucleotide variant
Location: chr10:60074870 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 (gnomAD)

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

Similar variants

ANK3 c.2382+6C>T Uncertain significance ★★ same type
ANK3 p.Ala1461Thr Uncertain significance ★★ ⚠ same type
ANK3 p.Ala1534Val Uncertain significance ★★ same type
ANK3 p.Ala1630Val Uncertain significance ★★ ⚠ same type
ANK3 p.Ala169Thr Uncertain significance ★★ same type
ANK3 p.Ala2023Thr Uncertain significance ★★ ⚠ same type
ANK3 p.Ala218Thr Uncertain significance ★★ same type
ANK3 p.Ala2223Thr Uncertain significance ★★ ⚠ same type

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-ala2004val (accessed [today's date]).

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