Is ANK3 p.Pro2070Ser (c.6208C>T) pathogenic?

ANK3 p.Pro2070Ser (c.6208C>T) is classified Uncertain significance in ANK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-02). AlphaMissense: likely pathogenic (0.8089); Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ANK3 p.Pro2070Ser (c.6208C>T)?

ANK3 p.Pro2070Ser (c.6208C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ANK3 p.Pro2070Ser (c.6208C>T) in the general population?

ANK3 p.Pro2070Ser (c.6208C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about ANK3 p.Pro2070Ser (c.6208C>T)?

AlphaMissense predicts likely pathogenic (score 0.8089) — an in-silico prediction, not a clinical call.

ANK3 p.Pro2070Ser

c.6208C>T · rs763122489 · VCV2332093

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8089 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8089	likely pathogenic
REVEL	0.284	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 5.3, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 7,641 bp · p 6.9e-05 · regional, not allelic
Overall
CADD	24.8	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 0.00017% European (non-Finnish) · 2/1,179,836 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,152 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.Pro2070Ser
Coding: c.6208C>T
MANE Select: NM_020987
dbSNP: rs763122489
Type: single nucleotide variant
Location: chr10:60074673 (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.Pro2070Leu 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
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-pro2070ser (accessed [today's date]).

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