Is ANK3 p.Ala3869Ser (c.11605G>T) pathogenic?

ANK3 p.Ala3869Ser (c.11605G>T) is classified Uncertain significance in ANK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-17). AlphaMissense: likely benign (0.1456); Very rare (popmax 8.47e-05%, nfe).

How common is ANK3 p.Ala3869Ser (c.11605G>T) in the general population?

ANK3 p.Ala3869Ser (c.11605G>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ANK3 p.Ala3869Ser (c.11605G>T)?

AlphaMissense predicts likely benign (score 0.1456) — an in-silico prediction, not a clinical call.

ANK3 p.Ala3869Ser

c.11605G>T · VCV4701798

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1456 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1456	likely benign
REVEL	0.143	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 5.9	GERP 5.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 1,310 bp · p 0.15 · regional, not allelic
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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) · 1/1,179,976 alleles

Overall 6.84e-05% 1/1,461,846 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.Ala3869Ser
Coding: c.11605G>T
MANE Select: NM_020987
Type: single nucleotide variant
Location: chr10:60069276 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 (gnomAD)
Residue 3869: the 'disordered' region

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-ala3869ser (accessed [today's date]).

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