Is ANK3 p.Arg31Pro (c.92G>C) pathogenic?

ANK3 p.Arg31Pro (c.92G>C) is classified Uncertain significance in ANK3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-02). AlphaMissense: ambiguous (0.4801); Ultra-rare (popmax 0.0329%, mid); Associated with Inborn genetic diseases.

What condition is associated with ANK3 p.Arg31Pro (c.92G>C)?

ANK3 p.Arg31Pro (c.92G>C) is associated with Inborn genetic diseases (ClinVar).

How common is ANK3 p.Arg31Pro (c.92G>C) in the general population?

ANK3 p.Arg31Pro (c.92G>C) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about ANK3 p.Arg31Pro (c.92G>C)?

AlphaMissense predicts ambiguous (score 0.4801) — an in-silico prediction, not a clinical call.

ANK3 p.Arg31Pro

c.92G>C · rs141511303 · VCV1514004

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4801 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4801	ambiguous
REVEL	0.317	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 110 kb · p 0.86 · regional, not allelic
Overall
CADD	24.2	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 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.00595% 96/1,613,840 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
African / African-American	0.0134%	7,487
Admixed American	0.0133%	7,498
Remaining individualsnot grpmax-eligible	0.0128%	7,810
South Asian	0.00878%	11,384
European (non-Finnish)	0.005%	19,999
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604

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.Arg31Pro
Coding: c.92G>C
MANE Select: NM_020987
dbSNP: rs141511303
Type: single nucleotide variant
Location: chr10:60389447 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 (gnomAD)
Residue 31: 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.Arg31Gln 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-arg31pro (accessed [today's date]).

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