Is KCNC1 p.Pro408= (c.1224G>A) pathogenic?

KCNC1 p.Pro408= (c.1224G>A) is classified Likely benign in KCNC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-05). Ultra-rare (popmax 0.0164%, mid); Associated with progressive myoclonic epilepsy type 7.

What condition is associated with KCNC1 p.Pro408= (c.1224G>A)?

KCNC1 p.Pro408= (c.1224G>A) is associated with progressive myoclonic epilepsy type 7 (ClinVar).

How common is KCNC1 p.Pro408= (c.1224G>A) in the general population?

KCNC1 p.Pro408= (c.1224G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Progressive myoclonic epilepsy type 7 inherited?

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

KCNC1 p.Pro408=

c.1224G>A · rs779961591 · VCV1152364

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

progressive myoclonic epilepsy type 7

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 -0.43	GERP -0.68, phastCons 0.006
Overall
CADD	11.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00204% 33/1,614,078 alleles · ultra-rare exomes 29/1,461,870 · genomes 4/152,208 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0032%	31,243
African / African-American	0.00267%	37,468
European (non-Finnish)	0.00229%	43,706
Finnishnot grpmax-eligible	0.00156%	64,012

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: KCNC1
Protein: p.Pro408=
Coding: c.1224G>A
MANE Select: NM_001112741
dbSNP: rs779961591
Type: single nucleotide variant
Location: chr11:17772318 (GRCh38)
Gene constraint: LOEUF 0.363 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 79.51 · 10 PDB

Full KCNC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

progressive myoclonic epilepsy type 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Progressive myoclonic epilepsy type 7 (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

KCNC1 p.Pro408Leu Uncertain significance ★ ⚠ same residue
KCNC1 p.Ala421Val Pathogenic/Likely pathogenic ★★ same condition
KCNC1 p.Arg320His Pathogenic/Likely pathogenic ★★ same condition
KCNC1 p.Thr399Met Pathogenic/Likely pathogenic ★★ same condition
KCNC1 p.Val425Met Pathogenic/Likely pathogenic ★★ same condition
KCNC1 p.Ala360Thr Uncertain significance ★★ ⚠ same condition
KCNC1 p.Ala418Ser Uncertain significance ★★ ⚠ same condition
KCNC1 p.Ala510Val 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/kcnc1-p-pro408 (accessed [today's date]).

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