Is ANK3 p.Met834Ile (c.2502G>A) pathogenic?

ANK3 p.Met834Ile (c.2502G>A) is classified Conflicting classifications of pathogenicity in ANK3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-01). AlphaMissense: ambiguous (0.3721); Absent from gnomAD v4.1.

How common is ANK3 p.Met834Ile (c.2502G>A) in the general population?

ANK3 p.Met834Ile (c.2502G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANK3 p.Met834Ile (c.2502G>A)?

AlphaMissense predicts ambiguous (score 0.3721) — an in-silico prediction, not a clinical call.

ANK3 p.Met834Ile

c.2502G>A · rs2132296500 · VCV1400314

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3721 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3721	ambiguous
REVEL	0.093	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 105 kb · p 5.9e-15 · regional, not allelic
Overall
CADD	24.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ANK3
Protein: p.Met834Ile
Coding: c.2502G>A
MANE Select: NM_020987
dbSNP: rs2132296500
Type: single nucleotide variant
Location: chr10:60166873 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 (gnomAD)

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-met834ile (accessed [today's date]).

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