Is ANK3 p.Pro359= (c.1077C>T) pathogenic?

ANK3 p.Pro359= (c.1077C>T) is classified Conflicting classifications of pathogenicity in ANK3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-12). Ultra-rare (popmax 0.0334%, eas); Associated with Inborn genetic diseases.

What condition is associated with ANK3 p.Pro359= (c.1077C>T)?

ANK3 p.Pro359= (c.1077C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ANK3 p.Pro359= (c.1077C>T) in the general population?

ANK3 p.Pro359= (c.1077C>T) is ultra-rare (popmax 0.0334%, eas) (gnomAD).

ANK3 p.Pro359=

c.1077C>T · rs747014545 · VCV210140

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.4	GERP -4.2
Overall
CADD	2.711	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0334% East Asian · 15/44,878 alleles

Filtering AF 0.0206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.00204% 33/1,614,084 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0334%	2,992
African / African-American	0.00533%	18,760
Admixed American	0.005%	20,004
Remaining individualsnot grpmax-eligible	0.0032%	31,254
European (non-Finnish)	0.000763%	131,109

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.Pro359=
Coding: c.1077C>T
MANE Select: NM_020987
dbSNP: rs747014545
Type: single nucleotide variant
Location: chr10:60208153 (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.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
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-pro359 (accessed [today's date]).

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