Is KCNA1 p.Pro244= (c.732C>T) pathogenic?

KCNA1 p.Pro244= (c.732C>T) is classified Likely benign in KCNA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-16). Very rare (popmax 0.00333%, amr); Associated with episodic ataxia type 1.

What condition is associated with KCNA1 p.Pro244= (c.732C>T)?

KCNA1 p.Pro244= (c.732C>T) is associated with episodic ataxia type 1 (ClinVar).

How common is KCNA1 p.Pro244= (c.732C>T) in the general population?

KCNA1 p.Pro244= (c.732C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

How is Episodic ataxia type 1 inherited?

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

KCNA1 p.Pro244=

c.732C>T · rs769026957 · VCV1107879

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

episodic ataxia type 1

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 4.1	GERP 1.9, phastCons 1
Overall
CADD	10.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,998 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000186% 3/1,614,032 alleles · very rare exomes 1/1,461,882 · genomes 2/152,150 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,999
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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: KCNA1
Protein: p.Pro244=
Coding: c.732C>T
MANE Select: NM_000217
dbSNP: rs769026957
Type: single nucleotide variant
Location: chr12:4912110 (GRCh38)
Gene constraint: LOEUF 0.935 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.74
Residue 244: a UniProt-annotated variant site (in mk1; does not affect channel activity)

Full KCNA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

episodic ataxia type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Episodic ataxia type 1 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Childhood

Similar variants

KCNA1 p.Pro244Ser Likely pathogenic ★ same residue
KCNA1 p.Pro244Leu Uncertain significance ★ ⚠ same residue
KCNA1 p.Pro244His Pathogenic same residue
KCNA1 p.Ala166Thr Likely pathogenic ★★ same condition
KCNA1 p.Arg417Ter Pathogenic ★★ same condition
KCNA1 p.Glu283Lys Pathogenic ★★ same condition
KCNA1 p.Gly396Val Pathogenic/Likely pathogenic ★★ same condition
KCNA1 p.Ile262Thr 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/kcna1-p-pro244 (accessed [today's date]).

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