Is ANK3 p.Leu3218Phe (c.9652C>T) pathogenic?

ANK3 p.Leu3218Phe (c.9652C>T) is classified Likely pathogenic in ANK3 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely benign (0.0838); Absent from gnomAD v4.1; Associated with Abnormal brain morphology.

What condition is associated with ANK3 p.Leu3218Phe (c.9652C>T)?

ANK3 p.Leu3218Phe (c.9652C>T) is associated with Abnormal brain morphology (ClinVar).

How common is ANK3 p.Leu3218Phe (c.9652C>T) in the general population?

ANK3 p.Leu3218Phe (c.9652C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANK3 p.Leu3218Phe (c.9652C>T)?

AlphaMissense predicts likely benign (score 0.0838) — an in-silico prediction, not a clinical call.

ANK3 p.Leu3218Phe

c.9652C>T · rs1060499742 · VCV402146

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0838 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Abnormal brain morphology

Computational evidence

Protein change
AlphaMissense	0.0838	likely benign ⚠ discordant with ClinVar
REVEL	0.054	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 0.34	GERP -1.2, phastCons 0.81
Regional constraint	o/e 0.92	unconstrained · MANE · 4,360 bp · p 0.0017 · regional, not allelic
Overall
CADD	16.39	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.Leu3218Phe
Coding: c.9652C>T
MANE Select: NM_020987
dbSNP: rs1060499742
Type: single nucleotide variant
Location: chr10:60071229 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 (gnomAD)
Residue 3218: the 'disordered' region

Full ANK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Abnormal brain morphology — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-leu3218phe (accessed [today's date]).

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