Is SLC12A5 p.Lys89fs (c.266del) pathogenic?

SLC12A5 p.Lys89fs (c.266del) is classified Pathogenic in SLC12A5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-01-14). No allele count reported in gnomAD v4.1 (AN 1,574,174); Associated with developmental and epileptic encephalopathy, 34.

What condition is associated with SLC12A5 p.Lys89fs (c.266del)?

SLC12A5 p.Lys89fs (c.266del) is associated with developmental and epileptic encephalopathy, 34 (ClinVar).

How common is SLC12A5 p.Lys89fs (c.266del) in the general population?

SLC12A5 p.Lys89fs (c.266del) is no allele count reported in gnomAD v4.1 (AN 1,574,174) (gnomAD).

SLC12A5 p.Lys89fs

Q: How is Epilepsy of infancy with migrating focal seizures inherited?

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

c.266del · rs2084489672 · VCV856637

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,574,174)

Conditions

developmental and epileptic encephalopathy, 34

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 3 of 26
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.4	GERP 2.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,574,174). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SLC12A5
Protein: p.Lys89fs
Coding: c.266del
MANE Select: NM_020708
dbSNP: rs2084489672
Type: Deletion
Location: chr20:46035517 (GRCh38)
Gene constraint: LOEUF 0.225 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.58 · 3 PDB

Full SLC12A5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 34 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Epilepsy of infancy with migrating focal seizures (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal

Similar variants

SLC12A5 c.52+21_52+35del Benign/Likely benign ★★ same condition
SLC12A5 p.Ala1053_Val1054insTer Pathogenic ★ same condition
SLC12A5 p.Asn229fs Pathogenic ★ same condition
SLC12A5 p.Glu965fs Pathogenic ★ same condition
SLC12A5 p.Gly181fs Pathogenic ★ same condition
SLC12A5 p.His768fs Pathogenic ★ same condition
SLC12A5 p.Leu766fs Pathogenic ★ same condition
SLC12A5 p.Leu840fs 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/slc12a5-p-lys89fs (accessed [today's date]).

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