Is CLCNKB p.Ser360= (c.1080G>A) pathogenic?

CLCNKB p.Ser360= (c.1080G>A) is classified Likely benign in CLCNKB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-31). Ultra-rare (popmax 0.0217%, nfe); Associated with Bartter disease type 3.

What condition is associated with CLCNKB p.Ser360= (c.1080G>A)?

CLCNKB p.Ser360= (c.1080G>A) is associated with Bartter disease type 3, Bartter disease type 4B (ClinVar).

How common is CLCNKB p.Ser360= (c.1080G>A) in the general population?

CLCNKB p.Ser360= (c.1080G>A) is ultra-rare (popmax 0.0217%, nfe) (gnomAD).

How is Bartter syndrome inherited?

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

CLCNKB p.Ser360=

c.1080G>A · rs140705060 · VCV1575391

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, nfe)

Conditions

Bartter disease type 3

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 -12	GERP -3.4
Overall
CADD	0.016	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0217% European (non-Finnish) · 256/1,179,912 alleles

Filtering AF 0.0195% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0186%

Overall 0.0204% 329/1,612,264 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.139%	722
Remaining individualsnot grpmax-eligible	0.0225%	4,452
European (non-Finnish)grpmax	0.0217%	4,609
Middle Eastern	0.0202%	4,960
Admixed American	0.015%	6,665
Finnishnot grpmax-eligible	0.0047%	21,281
African / African-American	0.00401%	24,939
East Asian	0.00223%	44,888
South Asian	0.0011%	91,016

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CLCNKB
Protein: p.Ser360=
Coding: c.1080G>A
MANE Select: NM_000085
dbSNP: rs140705060
Type: single nucleotide variant
Location: chr1:16050901 (GRCh38)
Gene constraint: LOEUF 1.072 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.16

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

Disease context

Bartter disease type 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bartter disease type 4B

For Bartter syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

CLCNKB p.Ser360Pro Uncertain significance ★ ⚠ same residue
CLCNKB p.Ser360Leu Uncertain significance ★ ⚠ same residue
CLCNKB c.968+1G>A Pathogenic/Likely pathogenic ★★ same condition
CLCNKB p.Ala204Thr Pathogenic/Likely pathogenic ★★ same condition
CLCNKB p.Arg304Ter Pathogenic/Likely pathogenic ★★ same condition
CLCNKB p.Arg438His Pathogenic ★★ same condition
CLCNKB p.Arg595Ter Pathogenic ★★ same condition
CLCNKB p.Arg76Ter 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/clcnkb-p-ser360 (accessed [today's date]).

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