Is ANK3 p.Ser1529Pro (c.4585T>C) pathogenic?

ANK3 p.Ser1529Pro (c.4585T>C) is classified Uncertain significance in ANK3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-20). AlphaMissense: ambiguous (0.4081); Ultra-rare (popmax 0.053%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ANK3 p.Ser1529Pro (c.4585T>C)?

ANK3 p.Ser1529Pro (c.4585T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ANK3 p.Ser1529Pro (c.4585T>C) in the general population?

ANK3 p.Ser1529Pro (c.4585T>C) is ultra-rare (popmax 0.053%, nfe) (gnomAD).

What do computational predictors say about ANK3 p.Ser1529Pro (c.4585T>C)?

AlphaMissense predicts ambiguous (score 0.4081) — an in-silico prediction, not a clinical call.

ANK3 p.Ser1529Pro

c.4585T>C · rs200919668 · VCV210162

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4081 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.053%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4081	ambiguous
REVEL	0.294	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	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	23.8	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 0.053% European (non-Finnish) · 625/1,179,982 alleles

Filtering AF 0.0495% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0482%

Overall 0.0395% 638/1,614,010 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.053%	1,888
Remaining individualsnot grpmax-eligible	0.0144%	6,943
African / African-American	0.00534%	18,728

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.Ser1529Pro
Coding: c.4585T>C
MANE Select: NM_020987
dbSNP: rs200919668
Type: single nucleotide variant
Location: chr10:60076296 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 (gnomAD)
Residue 1529: 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.Ser1529Cys Likely benign ★ same residue
ANK3 p.Ser1529Phe Uncertain significance ★★ 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

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-ser1529pro (accessed [today's date]).

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