Is KCNN2 p.Ser183Pro (c.547T>C) pathogenic?

KCNN2 p.Ser183Pro (c.547T>C) is classified Uncertain significance in KCNN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-20). Ultra-rare (popmax 0.0605%, sas); Associated with dystonia 34, myoclonic.

What condition is associated with KCNN2 p.Ser183Pro (c.547T>C)?

KCNN2 p.Ser183Pro (c.547T>C) is associated with dystonia 34, myoclonic, neurodevelopmental disorder with or without variable movement or behavioral abnormalities (ClinVar).

How common is KCNN2 p.Ser183Pro (c.547T>C) in the general population?

KCNN2 p.Ser183Pro (c.547T>C) is ultra-rare (popmax 0.0605%, sas) (gnomAD).

KCNN2 p.Ser183Pro

c.547T>C · VCV3362336

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0605%, sas)

Conditions

dystonia 34, myoclonic

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 0.44	GERP -2.5, phastCons 0.99
Regional constraint	o/e 1.47	unconstrained · MANE · 967 bp · p 3.7e-14 · regional, not allelic
Overall
CADD	18.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0605% South Asian · 42/69,416 alleles

Filtering AF 0.0459% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0409%

Overall 0.00324% 47/1,448,482 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0605%	1,653
Remaining individualsnot grpmax-eligible	0.00891%	11,223

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: KCNN2
Protein: p.Ser183Pro
Coding: c.547T>C
MANE Select: NM_021614
Type: single nucleotide variant
Location: chr5:114362686 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 77.98 · 16 PDB
Residue 183: a UniProt-annotated variant site (in nedmab)

Full KCNN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dystonia 34, myoclonic — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neurodevelopmental disorder with or without variable movement or behavioral abnormalities

Similar variants

KCNN2 p.Ser183Ter Likely pathogenic ★ same residue
KCNN2 p.Tyr573Cys Pathogenic/Likely pathogenic ★★ same condition
KCNN2 p.Gln15Ter Uncertain significance ★★ same condition
KCNN2 p.Leu644Pro Pathogenic ★ same condition
KCNN2 p.Trp562Leu Likely pathogenic ★ same condition
KCNN2 p.Tyr372Ter Pathogenic ★ same condition
KCNN2 p.Arg425His Uncertain significance ★ ⚠ same condition
KCNN2 p.Arg745Gly 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/kcnn2-p-ser183pro (accessed [today's date]).

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