Is KCNJ2 p.Phe331= (c.993T>C) pathogenic?

KCNJ2 p.Phe331= (c.993T>C) is classified Likely benign in KCNJ2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-13). Very rare (popmax 8.47e-05%, nfe); Associated with Andersen-Tawil syndrome.

What condition is associated with KCNJ2 p.Phe331= (c.993T>C)?

KCNJ2 p.Phe331= (c.993T>C) is associated with Andersen-Tawil syndrome, short QT syndrome type 3 (ClinVar).

How common is KCNJ2 p.Phe331= (c.993T>C) in the general population?

KCNJ2 p.Phe331= (c.993T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Andersen-Tawil syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

KCNJ2 p.Phe331=

c.993T>C · rs2509921601 · VCV2951907

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Andersen-Tawil syndrome

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 -1.9	GERP -4.3
Overall
CADD	5.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,008 alleles

Overall 6.84e-05% 1/1,461,878 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: KCNJ2
Protein: p.Phe331=
Coding: c.993T>C
MANE Select: NM_000891
dbSNP: rs2509921601
Type: single nucleotide variant
Location: chr17:70176032 (GRCh38)
Gene constraint: LOEUF 0.651 · pLI 0.38 (gnomAD)
Structure: AlphaFold pLDDT 82.15 · 3 PDB

Full KCNJ2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Andersen-Tawil syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: short QT syndrome type 3

For Andersen-Tawil syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

KCNJ2 p.Arg189Gly Likely pathogenic ★★ same condition
KCNJ2 p.Arg218Gln Pathogenic ★★ same condition
KCNJ2 p.Arg218Pro Likely pathogenic ★★ same condition
KCNJ2 p.Arg218Trp Pathogenic/Likely pathogenic ★★ same condition
KCNJ2 p.Arg260His Likely pathogenic ★★ same condition
KCNJ2 p.Arg312Cys Pathogenic/Likely pathogenic ★★ same condition
KCNJ2 p.Arg312His Pathogenic/Likely pathogenic ★★ same condition
KCNJ2 p.Arg67Gln Pathogenic/Likely pathogenic ★★ 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/kcnj2-p-phe331 (accessed [today's date]).

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