Is ANK3 p.Ala1534Val (c.4601C>T) pathogenic?

ANK3 p.Ala1534Val (c.4601C>T) is classified Uncertain significance in ANK3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-08-23). AlphaMissense: likely benign (0.2461); Very rare (popmax 0.00314%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ANK3 p.Ala1534Val (c.4601C>T)?

ANK3 p.Ala1534Val (c.4601C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ANK3 p.Ala1534Val (c.4601C>T) in the general population?

ANK3 p.Ala1534Val (c.4601C>T) is very rare (popmax 0.00314%, nfe) (gnomAD).

What do computational predictors say about ANK3 p.Ala1534Val (c.4601C>T)?

AlphaMissense predicts likely benign (score 0.2461) — an in-silico prediction, not a clinical call.

ANK3 p.Ala1534Val

c.4601C>T · rs187577622 · VCV1360351

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2461 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00314%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2461	likely benign
REVEL	0.31	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 5.4, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 7,641 bp · p 6.9e-05 · regional, not allelic
Overall
CADD	25.9	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 0.00314% European (non-Finnish) · 37/1,179,976 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00229% 37/1,614,146 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.Ala1534Val
Coding: c.4601C>T
MANE Select: NM_020987
dbSNP: rs187577622
Type: single nucleotide variant
Location: chr10:60076280 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 (gnomAD)
Residue 1534: the 'disordered' region

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.Ala1534= Likely benign ★ same residue
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-ala1534val (accessed [today's date]).

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