Is KCNMA1 p.Cys495= (c.1485C>T) pathogenic?

KCNMA1 p.Cys495= (c.1485C>T) is classified Likely benign in KCNMA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-13). Very rare (popmax 0.00878%, sas); Associated with generalized epilepsy-paroxysmal dyskinesia syndrome.

What condition is associated with KCNMA1 p.Cys495= (c.1485C>T)?

KCNMA1 p.Cys495= (c.1485C>T) is associated with generalized epilepsy-paroxysmal dyskinesia syndrome (ClinVar).

How common is KCNMA1 p.Cys495= (c.1485C>T) in the general population?

KCNMA1 p.Cys495= (c.1485C>T) is very rare (popmax 0.00878%, sas) (gnomAD).

KCNMA1 p.Cys495=

Q: How is Generalized epilepsy-paroxysmal dyskinesia syndrome inherited?

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

c.1485C>T · rs200500216 · VCV1122619

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

Conditions

generalized epilepsy-paroxysmal dyskinesia syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.218	benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.87	GERP -2.3, phastCons 1
Overall
CADD	12.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00878% South Asian · 8/91,084 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00345%

Overall 0.00421% 68/1,613,982 alleles · very rare exomes 63/1,461,782 · genomes 5/152,200 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00878%	11,386
European (non-Finnish)	0.00483%	20,701
East Asian	0.00223%	44,896
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-American	0.00133%	74,926

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: KCNMA1
Protein: p.Cys495=
Coding: c.1485C>T
MANE Select: NM_001161352
dbSNP: rs200500216
Type: single nucleotide variant
Location: chr10:77084675 (GRCh38)
Gene constraint: LOEUF 0.331 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.94 · 36 PDB
Residue 495: the rck n-terminal 1 domain; a UniProt-annotated variant site (in cadeds)

Full KCNMA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

generalized epilepsy-paroxysmal dyskinesia syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Generalized epilepsy-paroxysmal dyskinesia syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

KCNMA1 p.Cys495Arg Uncertain significance ★ ⚠ same residue
KCNMA1 p.Asn1053Ser Pathogenic ★★ same condition
KCNMA1 c.2015+5G>C Uncertain significance ★★ same condition
KCNMA1 c.378+5C>A Uncertain significance ★★ same condition
KCNMA1 p.Ala1049Thr Uncertain significance ★★ ⚠ same condition
KCNMA1 p.Ala1081Thr Uncertain significance ★★ same condition
KCNMA1 p.Ala138Pro Uncertain significance ★★ ⚠ same condition
KCNMA1 p.Ala154Ser 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/kcnma1-p-cys495 (accessed [today's date]).

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